[leish-l] Fwd: Articles found by RefScout 2005/10/05 - 2005/40

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This is RefScout-Newsletter 40/2005.






REQUEST: [ leishmaniasis ]

(18 articles match this request)



PMID: 16083969
 

TITLE: Activated inflammatory T cells correlate with lesion size in human
cutaneous leishmaniasis.

AUTHORS: Lis R V Antonelli, Walderez O Dutra, Roque P Almeida, Olivia Bacellar,
Edgar M Carvalho, Kenneth J Gollob

AFFILIATION: Department of Biochemistry-Immunology, Institute of Biological
Sciences-Federal University of Minas Gerais (UFMG-ICB), Av. Antonio Carlos,
6627 Belo Horizonte, MG 31640-970, Brazil.

REFERENCE: Immunol Lett 2005 Nov 101(2):226-30

Leishmaniasis is an important parasitic disease affecting millions 
worldwide. In attempts to understand the clinical relevance of 
immunological measurements as determined using flow cytometry, several 
immunological phenotypes were determined for a group of well defined 
human leishmaniasis patients and correlated with clinical measurements 
of the disease (Montenegro skin test (MST) and lesion area). The 
analysis demonstrated a positive correlation between the MST size and 
the frequency of ex vivo recent activated CD4(+) T cells. In contrast, 
higher frequencies of recent activated CD8(+) T cells were correlated 
with a smaller MST size. Moreover, a positive correlation was observed 
between the lesion total area and the frequency of activated CD69(+) (ex
 vivo) and CD40L(+) (cultured with Leishmania soluble antigen (SLA)) T 
lymphocytes. Finally, larger lesions were also correlated with a higher 
frequency of SLA specific inflammatory cytokine (IFN-gamma or TNF-alpha
) producing lymphocytes. These studies demonstrate that immunological 
markers are correlated with clinical indicators of human leishmaniasis 
and serve to better understand the evolution of this important parasitic
 disease.








PMID: 16192439
 

TITLE: Identification and antimicrobial susceptibility of micro-organisms
recovered from cutaneous lesions of human American tegumentary leishmaniasis in
Minas Gerais, Brazil.

AUTHORS: Claúdia O Fontes, Maria Auxiliadora R Carvalho, Jacques R Nicoli,
Junia S Hamdan, Wilson Mayrink, Odair Genaro, Luiz S Carmo, Luiz M Farias

AFFILIATION: Departamento de Microbiologia and Departamento de Parasitologia,
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, C.P.
486, 30161-970, Belo Horizonte, Minas Gerais, Brazil.

REFERENCE: J Med Microbiol 2005 Nov 54(Pt 11):1071-6

An evaluation of the microbiota present in cutaneous ulcers from 31 
patients with a clinical and parasitological diagnosis of American 
tegumentary leishmaniasis (ATL) was carried out by the standard filter 
paper disc technique, including antimicrobial susceptibility of the 
bacterial isolates. Microbial examination indicated that 21 patients (67
.7 %) were contaminated with one to four bacteria and some of them also 
with yeast. A total of 142 micro-organisms were isolated. Staphylococcus
 aureus was the most frequently recovered bacterium (95.2 % of positive 
patients) and was found to produce type B (70 % of the staphylococcal 
isolates) and type C (50 %) enterotoxins as well as toxic shock syndrome
 toxin (60 %). Proteus mirabilis (33.3 % of the positive patients), 
Streptococcus pyogenes (19.0 %), H(2)S-negative Proteus species (19.0
 %), Klebsiella oxytoca (14.3 %), Enterobacter species (9.5 %), 
Peptostreptococcus species (9.5 %), Pseudomonas species (4.8 %), 
Prevotella bivia (4.8 %), Escherichia coli (4.8 %), Streptococcus 
agalactiae (4.8 %), Bacteroides fragilis (4.8 %), Candida albicans (9.5
 %) and Candida tropicalis (4.8 %) were also isolated. Surprisingly, 
Staph. aureus isolates were susceptible to almost all tested drugs, 
although some of them were resistant to penicillin (69 %) and ampicillin
 + sulbactam (68 %). Concerning obligate anaerobes, all the Gram-
negative isolates (25 % of the total) were resistant to metronidazole. 
The results of the present study show that microbial secondary 
contaminants, particularly Staph. aureus, should be considered in the 
diagnosis and treatment of ATL lesions.




PMID: 16177308
 

TITLE: Live nonpathogenic parasitic vector as a candidate vaccine against
visceral leishmaniasis.

AUTHORS: Marie Breton, Michel J Tremblay, Marc Ouellette, Barbara Papadopoulou

AFFILIATION: Infectious Diseases Research Center, CHUL Research Center of Laval
University, Quebec, Canada.

REFERENCE: Infect Immun 2005 Oct 73(10):6372-82

To date, there are no proven vaccines against any form of leishmaniasis
. The development of live attenuated vectors shows promise in the field 
of Leishmania vaccination because these organisms mimic more effectively
 the course of real infections and can elicit potent activation of the 
immune system. In the present study, we investigated the potential of a 
parasitic protozoan that is nonpathogenic to humans, Leishmania 
tarentolae, as a live candidate vaccine that efficiently targets 
dendritic cells and lymphoid organs, thus enhancing antigen presentation
 and consequently influencing the magnitude and quality of T-cell immune
 responses. We demonstrated that L. tarentolae activates the dendritic 
cell maturation process and induces T-cell proliferation and the 
production of gamma interferon, thus skewing CD4(+) T cells toward a Th1
 cell phenotype. More importantly, we found that a single 
intraperitoneal injection of L. tarentolae could elicit a protective 
immune response against infectious challenge with Leishmania donovani in
 susceptible BALB/c mice. These results suggest that the use of L. 
tarentolae as a live vaccine vector may represent a promising approach 
for improving the effectiveness and safety of candidate live vaccines 
against Leishmania infections and possibly other intracellular pathogens
 for which T-cell mediated responses are critical for the development of
 protective immunity.




PMID: 16177384
 

TITLE: Identification of new antigens in visceral leishmaniasis by expression
cloning and immunoblotting with sera of kala-azar patients from Bihar, India.

AUTHORS: Stephan M Theinert, Rajatava Basu, Michael Forgber, Syamal Roy, Shyam
Sundar, Peter Walden

AFFILIATION: Clinical Research Group, Department of Dermatology, Charité
University Medicine Berlin, Humboldt University, Germany.

REFERENCE: Infect Immun 2005 Oct 73(10):7018-21

Sera of kala-azar patients from Bihar, India, were used to identify 
Leishmania donovani antigens encoded by a phage expression library. Ten 
antigens were identified, five of which have not been described as 
leishmania antigens before. The antigens specifically react with sera of
 leishmania-infected patients but not of toxoplasma- or plasmodium-
infected patients.




PMID: 16184223
 

TITLE: Lutzomyia longipalpis in Clorinda, Formosa province, an area of potential
visceral leishmaniasis transmission in Argentina.

AUTHORS: Oscar D Salomón, Pablo W Orellano

AFFILIATION: Centro Nacional de Diagnóstico e Investigación en
Endemo-Epidemias, ANLIS, Ministerio de Salud y Ambiente de la Nación, Buenos
Aires, Argentina. danielsalomon at hotmail.com

REFERENCE: Mem Inst Oswaldo Cruz 2005 Aug 100(5):475-6

Phlebotomine captures were performed during 2004 in Clorinda, Argentina
. Clorinda is located across the branches of the Paraguay river in front
 of Asunción city, Paraguay. Reports of canine and human visceral 
leishmaniasis in Asunción have been increasing since 1997, however 
neither leishmaniasis cases nor sand flies were ever recorded from 
Clorinda. Light traps were located in migration paths (bridges, port), 
and peridomestic environments of Clorinda and surrounding localities. 
Lutzomyia longipalpis was found in Clorinda and Puerto Pilcomayo, first 
report in a potential visceral leishmaniasis transmission area for 
Argentina. Active surveillance is required immediately in the localities
 involved and the surrounding area.




PMID: 16184231
 

TITLE: Further observations on clinical, histopathological, and immunological
features of borderline disseminated cutaneous leishmaniasis caused by
Leishmania (Leishmania) amazonensis.

AUTHORS: Fernando T Silveira, Ralph Lainson, Carlos E P Corbett

AFFILIATION: Departamento de Parasitologia, Instituto Evandro Chagas, Belém,
PA, 66090-000, Brazil. fernandotobias at iec.pa.gov.br

REFERENCE: Mem Inst Oswaldo Cruz 2005 Aug 100(5):525-34

Leishmania (Leishmania) amazonensis has for some time been considered as
 the causative agent of two distinct forms of American cutaneous 
leishmaniasis (ACL): localized cutaneous leishmaniasis (LCL), and 
anergic diffuse cutaneous leishmaniasis (ADCL). Recently, a new 
intermediate form of disease, borderline disseminated cutaneous 
leishmaniasis (BDCL), was introduced into the clinical spectrum of ACL 
caused by this parasite, and in this paper we record the clinical, 
histopathological, and immunological features of eight more BDCL 
patients from Brazilian Amazonia, who acquired the disease in the Pará 
state, North Brazil. Seven of them had infections of one to two years' 
evolution and presented with primary skin lesions and the occurrence of 
metastases at periods varying from six to 12 months following appearance
 of the first lesion. Primary skin lesions ranged from 1-3 in number, 
and all had the aspect of an erythematous, infiltrated plaque, variously
 located on the head, arms or legs. There was lymphatic dissemination of
 infection, with lymph node enlargement in seven of the cases, and the 
delayed hypersensitivity skin-test (DTH) was negative in all eight 
patients prior to their treatment. After that, there was a conversion of
 DTH to positive in five cases re-examined. The major histopathological 
feature was a dermal mononuclear infiltration, with a predominance of 
heavily parasitized and vacuolated macrophages, together with 
lymphocytes and plasma cells. In one case, with similar histopathology, 
the patient had acquired his infection seven years previously and he 
presented with the largest number of disseminated cutaneous lesions. 
BDCL shows clinical and histopathological features which are different 
from those of both LCL and ADCL, and there is a good prognosis of cure 
which is generally not so in the case of frank ADCL.




PMID: 15882412
 

TITLE: LmxPK4, a mitogen-activated protein kinase kinase homologue of Leishmania
mexicana with a potential role in parasite differentiation.

AUTHORS: Daniela Kuhn, Martin Wiese

AFFILIATION: Bernhard Nocht Institute for Tropical Medicine, Parasitology
Section, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.

REFERENCE: Mol Microbiol 2005 Jun 56(5):1169-82

Members of the mitogen-activated protein (MAP) kinase cascade are 
important for the establishment of a Leishmania mexicana infection and 
are involved in flagellar length control, although the underlying 
molecular mechanisms remain to be elucidated. This study reports the 
cloning and characterization of LmxPK4, a MAP kinase kinase homologue of
 L. mexicana displaying putative plant-like regulatory phosphorylation 
sites. The recombinant protein has autophosphorylating activity and 
phosphorylates myelin basic protein. An LmxPK4 gene deletion mutant 
showed a proliferation defect after infection of macrophages and no or 
delayed lesion development in mice. Irrespective of the onset of lesion 
development parasites showed an early and homogeneous lesion development
 in re-infection experiments. This is indicative for a compensation of 
the null mutant phenotype. Additionally, this phenotype could be 
reverted by reintroduction of the wild-type gene into the deletion 
background. Mutants expressing loss-of-function or N-terminally 
truncated versions of LmxPK4 retained the null mutant phenotype. LmxPK4 
is stage-specifically expressed in promastigotes and during 
differentiation to amastigotes, but is not detectable in amastigotes 
isolated from the mammalian host. Moreover, its in vitro kinase activity
 increases with temperature rise up to 40 degrees C. Our results suggest
 that LmxPK4 is involved in the differentiation process and affects 
virulence of Leishmania mexicana.




PMID: 16199372
 

TITLE: Targeting of mannosylated liposome incorporated benzyl derivative of
Penicillium nigricans derived compound MT81 to reticuloendothelial systems for
the treatment of visceral leishmaniasis.

AUTHORS: Maitreyi Mitra, Ardhendu K Mandal, Tapan Kumar Chatterjee, Nirmalendu
Das

AFFILIATION: Jadavpur University, Department of Pharmaceutical Technology,
Kolkata, 700 032, India.

REFERENCE: J Drug Target 2005 Jun 13(5):285-93

The antileishmanial property of a Benzyl derivative of a new antibiotic 
MT81 (Bz(2)MT81), isolated and purified from a fungal strain of 
Penicillium nigricans NRRL 917 was tested in free, liposome intercalated
 and mannose coated liposome intercalated forms in vivo against visceral
 leishmaniasis in hamsters. Mannose grafted liposome intercalated Bz(2)
MT81 eliminated intracellular amastigotes of Leishmania donovani within 
splenic macrophages more efficiently than the liposome intercalated Bz(2
)MT81 or free Bz(2)MT81. At a dose equivalent to 7.5 mug/Kg body weight 
when injected subcutaneously (s.c) in mannose grafted liposome 
intercalated form for 15 days in an interval of three days, the splenic 
parasitic load decreased to the extent of 79.1% of the total parasite 
present in infected control animals. Whereas, an identical amount (7.5 
mug/Kg body weight) of Bz(2)MT81 in free or liposome intercalated form 
was found less effective in controlling the parasite in spleen (in free 
Bz(2)MT81 form, suppression of parasitic load is 49.8% and in liposome 
intercalated form, it is 55.1%). Both mannosylated liposomes and Bz(2)
MT81 were noted non-toxic to the host peritoneal macrophages. 
Histological examinations of spleen and liver, kidney function tests (
SGPT, alkaline phosphatase, creatinine and urea in blood plasma) showed 
that the toxicity of Bz(2)MT81 was reduced up to normal level when 
mannose grafted liposomal Bz(2)MT81 were administered.








PMID: 16178749
 

TITLE: Dihidro-beta-agarofuran sesquiterpenes: a new class of reversal agents of
the multidrug resistance phenotype mediated by P-glycoprotein in the protozoan
parasite Leishmania.

AUTHORS: F Cortés-Selva, I A Jiménez, F Munoz-Martínez, M Campillo, I L
Bazzocchi, L Pardo, A G Ravelo, S Castanys, F Gamarro

AFFILIATION: Instituto de Parasitología y Biomedicina López-Neyra, Consejo
Superior de Investigaciones Científicas, Parque Tecnológico de Ciencias de la
Salud, Avda. del Conocimiento s/n, 18100-Armilla, Granada, Spain.

REFERENCE: Curr Pharm Des 2005  11(24):3125-39

Leishmaniasis is the most important emerging and uncontrolled infectious
 disease and the second cause of death among parasitic diseases, after 
Malaria. One of the main problems concerning the control of infectious 
diseases is the increased resistance to usual drugs. Overexpression of P
-glycoprotein (Pgp)-like transporters represents a very efficient 
mechanism to reduce the intracellular accumulation of drugs in cancer 
cells and parasitic protozoans, thus conferring a multidrug resistance (
MDR) phenotype. Pgps are active pumps belonging to the ATP-binding 
cassette (ABC) superfamily of proteins. The inhibition of the activity 
of these proteins represents an interesting way to control drug 
resistance both in cancer and in infectious diseases. Most conventional 
mammalian Pgp-MDR modulators are ineffective in the modulation of Pgp 
activity in the protozoan parasite Leishmania. Consequently, there is a 
necessity to find effective modulators of Pgp-MDR for protozoan 
parasites. In this review we describe a rational strategy developed to 
find specific Pgp-MDR modulators in Leishmania, using natural and 
semisynthetic dihydro-beta-agarofuran sesquiterpenes from Celastraceae 
plants. A series of these compounds have been tested on a MDR Leishmania
 tropica line overexpressing a Pgp transporter to determine their 
ability to revert the resistance phenotype and to modulate intracellular
 drug accumulation. Almost all of these natural compounds showed potent 
reversal activity with different degrees of selectivity and a 
significant low toxicity. The three-dimensional quantitative structure-
activity relationship using the comparative molecular similarity indices
 analysis (CoMSIA), was employed to characterize the requirements of 
these sesquiterpenes as modulators at Pgp-like transporter in Leishmania.




PMID: 16188725
 

TITLE: Designing and Testing of an Effective Oil-in-Water Microemulsion Drug
Delivery System for In Vivo Application.

AUTHORS: S Gupta, S P Moulik, S Lala, M K Basu, S K Sanyal, S Datta

AFFILIATION: Centre for Surface Science, Department of Chemistry, Jadavpur
University, Kolkata, India.

REFERENCE: Drug Deliv 2005 Sep-Oct 12(5):267-73

The phase behavior of a new psedoternary system of clove oil/Tween 20 
has been studied. Several compositions from the single-phase region were
 selected and their stability toward time, temperature, and electrolytes
 has been examined. A particular composition(clove oil/Tween 20/water as
 5/30/65) was chosen as the drug delivery system from the clear oil-in-
water zone of the pseudoternary system. The droplet dimension and the 
polydispersity state of the particular composition was determined by 
dynamic light scattering. A bioactive compound quarcetin was 
encapsulated in the vehicle. The efficacy of the drug in the vehicle was
 examined against leishmaniasis in hamster models. The hepatotoxicity of
 the vehicle (o/w microemulsion) with and without the drug quarcetin was
 examined by estimating serum alkaline phosphatase, glutamate pyruvate 
transaminase, urea, and creatinine.




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PMID: 12965912
 

TITLE: Enzyme-linked immunoassay using recombinant trans-sialidase of
Trypanosoma cruzi can be employed for monitoring of patients with Chagas'
disease after drug treatment.

AUTHORS: Vera Lucia Pereira-Chioccola, Abilio Augusto Fragata-Filho, Antonio
Marcos de Apparecida Levy, Mauricio M Rodrigues, Sergio Schenkman

AFFILIATION: Laboratório de Parasitologia, Instituto Adolfo Lutz, São Paulo,
SP, Brazil. pchioccola at ial.sp.gov.br

REFERENCE: Clin Diagn Lab Immunol 2003 Sep 10(5):826-30

trans-Sialidase is an enzyme present on the surface of Trypanosoma cruzi
 and is an important antigen recognized by sera from patients with 
Chagas' disease. In the present study we investigated whether the 
benznidazole treatment of patients with Chagas' disease induced changes 
in the reactivity of serum toward a recombinant form of trans-sialidase 
in order to develop an assay for monitoring of patients after treatment 
for Chagas' disease, which is needed at Chagas' disease control centers
. By using an enzyme-linked immunosorbent assay containing a recombinant
 protein corresponding to the catalytic domain of trans-sialidase, we 
found that the antigen had a high specificity for sera from untreated 
patients with Chagas' disease. Sera from healthy individuals or patients
 with active visceral leishmaniasis minimally cross-reacted with the 
antigen. Anti-trans-sialidase immunoglobulin was detected in 98% of 151 
untreated patients with Chagas' disease. Of these, 124 patients were 
treated for 60 days with benznidazole (5 mg/kg of body weight/day), and 
their sera were assayed for reactivity with the recombinant trans-
sialidase. By using this methodology, three groups of patients could be 
established. The first group (60 patients), which was considered to have
 been successfully treated, showed no reactivity after treatment. The 
second group (46 patients) still showed signs of infection, and after 
treatment their sera recognized trans-sialidase, but with reduced titers
. The third group (18 patients) was considered to be resistant to drug 
treatment, and their sera presented identical reactivities before and 
after treatment. These results suggest that determination of the absence
 of antibodies to recombinant trans-sialidase in treated patients by the
 present assay is indicative of treatment success, while the presence of
 antibodies may indicate the persistence of infection. Therefore, this 
method may be useful for the diagnosis and monitoring of patients 
undergoing benznidazole treatment.




PMID: 12793911
 

TITLE: In vitro antileishmanial effects of antibacterial diterpenes from two
Ethiopian Premna species: P. schimperi and P. oligotricha.

AUTHORS: Solomon Habtemariam

AFFILIATION: Pharmacognosy & Phytotherapy Research Laboratory, School of
Chemical and Life Sciences, the University of Greenwich at Medway, Central
Avenue, Chatham Maritime, Kent ME4 4TB, UK. s.habtemariam at gre.ac.uk

REFERENCE: BMC Pharmacol 2003 Jun 3():6

BACKGROUND: Three antibacterial diterpenes: (5R,8R,9S,10R)-12-oxo-ent-3,
13(16)-clerodien-15-oic acid (1), 16-hydroxy-clerod-3,13(14)-diene-15,16
-olide (2) and ent-12-oxolabda-8,13(16)-dien-15-oic acid (3) were 
previously isolated form Premna schimperi and P. oligotricha. Since 
andrographolide and other structurally related diterpenes were shown to 
have antileishmanial activity, the aim of the present study was to 
assess the in vitro effect of premna diterpenes against Leishmania 
aethiopica; the causative agent of cutaneous leishmaniasis in Ethiopia. 
RESULTS: The diterpenes showed potent concentration-dependant 
suppressive effect on the viability of axenically cultured amastigotes 
of L. aethiopica. The clerodane diterpenes 1 and 2 were most active (
LD50 values 1.08 and 4.12 microg/ml respectively) followed by 
andrographolide and 3. Compounds 1 and 2 appear to be over 20 and 10-
times respectively more selective to leishmania amastigotes than the 
permissive host cell line, THP-1 cells or the promastigotes stage of the
 parasites. CONCLUSION: The clerodane diterpenes (1, 2) which were more 
potent and selective than labdanes (andrographolide and 3) are promising
 for further studies and/or development.




PMID: 12019027
 

TITLE: In vitro susceptibility to pentavalent antimony in Leishmania infantum
strains is not modified during in vitro or in vivo passages but is modified
after host treatment with meglumine antimoniate.

AUTHORS: Jaume Carrió, Montserrat Portús

AFFILIATION: Laboratory of Parasitology, Departament de Microbiologia i
Parasitologia Sanità ries, Facultat de Farmà cia, Universitat de Barcelona,
08028 Barcelona, Spain. jcarrio at farmacia.far.ub.es

REFERENCE: BMC Pharmacol 2002 May 2():11

BACKGROUND: Leishmaniasis is a common parasitic disease in Southern 
Europe, caused by Leishmania infantum. The failures of current treatment
 with pentavalent antimonials are partially attributable to the 
emergence of antimony-resistant Leishmania strains. This study analyses 
the in vitro susceptibility to pentavalent antimony of intracellular 
amastigotes from a range of L. infantum strains, derived from the same 
infected animal, during in vitro and in vivo passages and after host 
treatment with meglumine antimoniate. RESULTS: SbV-IC50 values for 
strains from two distinct isolates from the same host and one stock 
after two years of culture in NNN medium and posterior passage to 
hamster were similar (5.0 +/- 0.2; 4.9 +/- 0.2 and 4.4 +/- 0.1 mgSbV/L, 
respectively). In contrast, a significant difference (P < 0.01, t 
test) was observed between the mean SbV-IC50 values in the stocks 
obtained before and after treatment of hosts with meglumine antimoniate
 (4.7 +/- 0.4 mgSbV/L vs. 7.7 +/- 1.5 mgSbV/L). Drug-resistance after 
drug pressure in experimentally infected dogs increased over repeated 
drug administration (6.4 +/- 0.5 mgSbV/L after first treatment vs. 8.6
 +/- 1.4 mgSbV/L after the second) (P < 0.01, t test). CONCLUSIONS: 
These results confirm previous observations on strains from Leishmania/
HIV co-infected patients and indicate the effect of the increasing use 
of antimony derivatives for treatment of canine leishmaniasis in endemic
 areas on the emergence of Leishmania antimony-resistant strains.




PMID: 11139217
 

TITLE: trans-sialidase inhibition assay, a highly sensitive and specific
diagnostic test for Chagas' disease.

AUTHORS: A S Buchovsky, O Campetella, G Russomando, L Franco, R Oddone, N
Candia, A Luquetti, S M Gonzalez Cappa, M S Leguizamon

AFFILIATION: Departamento de Microbiología, Facultad de Medicina, Universidad
de Buenos Aires, Buenos Aires, Argentina.

REFERENCE: Clin Diagn Lab Immunol 2001 Jan 8(1):187-9

For the diagnosis of Chagas' disease, the trans-sialidase inhibition 
assay was able to resolve the results for samples with borderline 
results, to detect as positive 60% of samples that were negative by 
conventional serology, and to discriminate idiopathic from chagasic 
megaviscera or cardiopathy. No cross-reaction with sera from patients 
with other diseases was observed.




PMID: 11299045
 

TITLE: Flow cytometry analysis of the effect of allopurinol and the
dinitroaniline compound (Chloralin) on the viability and proliferation of
Leishmania infantum promastigotes.

AUTHORS: S W Kamau, R Nunez, F Grimm

AFFILIATION: Institute of Parasitology, University of Zurich, Switzerland.
skamau at vetparas.unizh.ch

REFERENCE: BMC Pharmacol 2001  1():1

BACKGROUND: Leishmaniasis is a major parasitic disease in the tropical 
regions. However, Leishmania infantum has recently emerged as a very 
important cause of opportunistic infections for individuals positive for
 human immunodeficiency virus (HIV). However, there is a lack of in 
vitro tests for assessing the effect of anti-parasitic drugs on the 
viability and proliferation of Leishmania infantum. The aim of this 
study is to assess the efficacy of anti-parasitic drugs like allopurinol
 and Chloralin on the viability and proliferation of L. infantum 
promastigotes by utilizing two complementary flow cytometric approaches 
after exposure of the promastigotes to various concentrations of the 
drugs. RESULTS: The density of the cultures in the presence and absence 
of allopurinol was determined by haemocytometer enumeration. The two 
flow cytometric approaches used to monitor the drug effect were: (i) a 
quantitative method to measure cell division using 5-,6-
carboxyfluorescein diacetate succinimidyl ester (CFSE) staining and (ii
) evaluation of cell viability by dual-staining with the membrane-
permeable nuclear stain, SBRY-14 and propidium iodide. It was found that
 concentrations of allopurinol above 50 microg/ml yielded a clear 
decrease in the proliferation rate of the promastigotes. However, the 
viability results showed that about 46.8% of the promastigotes incubated
 in the presence of 800 microg/ml of allopurinol were still alive after 
96 hours. In sharp contrast, more than 90% of promastigotes treated with
 Chloralin 10 microM (2.7 microg/ml) were dead after 48 hours of 
treatment. These flow cytometric findings suggest that allopurinol has a
 leishmaniostatic effect while the dinitroaniline compound (Chloralin) 
has a leishmaniocidal effect against promastigotes. CONCLUSIONS: The 
flow cytometric data on proliferation and viability were consistent with
 results obtained from haemocytometer counts and allowed us to develop a
 model for assessing in vitro the effects of medicaments like 
allopurinol and chloralin on L. infantum promastigotes on a cellular 
level.








PMID: 10768966
 

TITLE: Heterologous expression of Trypanosoma cruzi trans-sialidase in
Leishmania major enhances virulence.

AUTHORS: M Belen Carrillo, W Gao, M Herrera, J Alroy, J B Moore, S M Beverley, M
A Pereira

AFFILIATION: Parasitology Research Center, Department of Pathology, Tufts
University School of Medicine, Boston, Massachusetts 02111, USA.

REFERENCE: Infect Immun 2000 May 68(5):2728-34

Earlier studies showed that mice primed for a few hours with the trans-
sialidase (TS) of Trypanosoma cruzi, the agent of Chagas' disease, 
become highly susceptible to trypanosomal infection. These studies 
suggest that TS affects parasite virulence independent of antigenic 
stimulation. Potentially, TS could enhance or reduce the virulence of 
heterologous microbes depending on the mechanism of TS action and on the
 type of immune response elicited by the particular parasite. We tested 
this hypothesis by expressing heterologous TS in Leishmania major, a 
protozoan parasite that causes cutaneous leishmaniasis and lacks TS and 
the TS product alpha2-3-linked sialic acid. Leishmania cells transfected
 with a T. cruzi TS expression construct made high levels of active 
enzyme, which was present in the promastigotes and shed into the 
extracellular milieu. TS expression did not affect L. major binding to 
and entry into cultured macrophages or its tropism for macrophage 
infection in vivo. However, TS-expressing L. major exhibited elevated 
virulence in BALB/c mice, as determined by lesion progression, parasite 
numbers, and macro- and microscopic examination of cutaneous lesions. 
Several genetic tests proved that the enhanced virulence was directly 
attributable to TS expression. The results are consistent with TS 
functioning to sabotage the mouse immune system to confer a growth 
advantage on T. cruzi and transgenic L. major. These data suggest that 
heterologous expression of T. cruzi virulence factors in Leishmania may 
provide a new approach for dissecting their function in vivo.




PMID: 3909974
 

TITLE: The potential role of Leishmania antigens and immunoglobulins in the
pathogenesis of glomerular lesions of hamsters infected with Leishmania
donovani.

AUTHORS: A V Oliveira, M A Rossi, M C Rogue-Barreira, A Sartori, A Campos-Neto

REFERENCE: Ann Trop Med Parasitol 1985 Oct 79(5):539-43




PMID: 13386480
 

TITLE: [First case of cutaneous leishmaniasis seen in a native of Morocco
outside the Sahara zone.]

AUTHORS: M DEKESTER, P MELNOTTE

REFERENCE: Maroc Med 1956 Oct 35(377):973-4




REQUEST: [ leishmania ]

(23 articles match this request. 11 articles matching other requests removed)



PMID: 16125801
 

TITLE: Specific negative charges in cysteine protease isoforms of
Leishmaniamexicana are highly influential on the substrate binding and
hydrolysis.

AUTHORS: Wagner A S Judice, Jeremy C Mottram, Graham H Coombs, Maria A Juliano,
Luiz Juliano

AFFILIATION: Department of Biophysics, Escola Paulista de Medicina, Universidade
Federal de São Paulo, Rua Tres de Maio 100, 04044-20 São Paulo, Brazil.

REFERENCE: Mol Biochem Parasitol 2005 Nov 144(1):36-43

We focused on the importance of the electrostatic environment on the 
catalytic properties of the Leishmania mexicana CPB recombinant 
isoenzymes (rCPB2.8, rCPB3 and its mutant rH84Y), by investigating the 
influence of pH and NaCl on their hydrolytic activities. rCPB2.8 
contains the residues Asn60, Asp61 and Asp64; rCPB3 presents the three 
variant residues Asp60, Asn61 and Ser64 and the mutant of the latter 
isoform, rH84Y, has a mutation on the outer loop residue (His84 to Tyr
). Synthetic fluorescence resonance energy transfer (FRET) peptides, 
which contain different positive charge distribution in their sequences 
were used as substrates. The results show that hydrolytic efficiency is 
dependent of the positive charge distribution in the substrates and that
 NaCl activated rCPB2.8 and rCPB3 in acidic pH but inhibited them at pH 
higher than 5. The rate constants of substrate diffusion (k(1)), 
substrate dissociation (k(-1)), acylation (k(2)) and deacylation (k(3)) 
and the corresponding activation energies and entropies were derived. 
Significant differences in the kinetic rate constants (k) and entropies 
were found between the CPB isoforms, and the diffusion process seems to 
be the limiting step. The activation energy of denaturation (E(a-Den)) 
and entropy of denaturation (DeltaS(Den)) of rCPB3 were higher than 
those for rCPB2.8, suggesting higher salvation and protein structure for
 rCPB3. Thus the findings suggest that the two CPB isoenzymes with a few
 negative charge modifications provide the parasite with an array of 
hydrolytic activity and enzymatic adaptation to pH, salinity and 
temperature that may be needed for its interaction with the mammalian 
host.




PMID: 16169099
 

TITLE: Environmental kinetoplastid-like 18S rRNA sequences and phylogenetic
relationships among Trypanosomatidae: Paraphyly of the genus Trypanosoma.

AUTHORS: Helen Piontkivska, Austin L Hughes

AFFILIATION: Department of Biological Sciences, 242 Cunningham Hall, Kent State
University, Kent OH 44242, USA.

REFERENCE: Mol Biochem Parasitol 2005 Nov 144(1):94-9

Using kinetoplastid-like sequences from deep-sea environmental samples 
as an outgroup, we applied phylogenetic analysis to 18S rRNA sequences 
of the families Trypanosomatidae and Bodonidae (Eugelenozoa: 
Kinetoplastida). The monophyly of the genus Trypanosoma was not 
supported by a number of different methods. Rather, the results indicate
 that the American and African trypanosomes constitute distinct clades, 
therefore, implying that the major human disease agents T. cruzi (cause 
of Chagas' disease) and T. brucei (cause of African sleeping sickness) 
are not as closely related to each other as they were previously thought
 to be. Likewise, the results did not support monophyly of the genera 
Leishmania, Leptomonas, Bodo and Cryptobia.




PMID: 16189098
 

TITLE: Inhibition of hepatitis C virus replication by antimonial compounds.

AUTHORS: Der-Ren Hwang, Ren-Kuo Lin, Guang-Zhou Leu, Tiao-Yin Lin, Tzu-Wen Lien,
Ming-Chen Yu, Chau-Ting Yeh, John T-A Hsu

AFFILIATION: Division of Biotechnology and Pharmaceutical Research, National
Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350,
Taiwan, Republic of China. tsuanhsu at nhri.org.tw.

REFERENCE: Antimicrob Agents Chemother 2005 Oct 49(10):4197-202

Chronic hepatitis C virus (HCV) infection is a worldwide health problem 
causing serious complications, such as liver cirrhosis and hepatoma. 
Alpha interferon (IFN-alpha) or its polyethylene glycol-modified form 
combined with ribavirin is the only recommended therapy. However, an 
alternative therapy is needed due to the unsatisfactory cure rate of the
 IFN-based therapy. Using a modified reporter assay based on the HCV 
subgenomic-replicon system, we found that sodium stibogluconate (SSG), a
 compound used for leishmania treatment, suppressed HCV replication. We 
have previously reported that SSG is effective at inhibiting HCV 
replication in a cell line permissive for HCV infection/replication and 
in an ex vivo assay using fresh human liver slices obtained from 
patients infected with HCV (26). In this study, we show that the SSG 50
% inhibitory dose for HCV replication is 0.2 to 0.3 mg/ml (equivalent to
 345 to 517 muM of Sb) in the HCV subgenomic-replicon system. We also 
found that SSG and IFN-alpha exert a strong synergistic anti-HCV effect 
in both the traditional isobologram analysis and the median effect 
principle (CalcuSyn analysis). The combination of SSG and IFN-alpha 
could sustain the antiviral response better than SSG or IFN-alpha alone
. The results suggest that SSG may be a good drug candidate for use in 
combination with other therapeutics, such as IFN-alpha and ribavirin, to
 treat HCV infection.




PMID: 16189135
 

TITLE: Lower Nitric Oxide Susceptibility of Trivalent Antimony-Resistant
Amastigotes of Leishmania infantum.

AUTHORS: P Holzmuller, D Sereno, J-L Lemesre

AFFILIATION: UR 008 Pathogénie des Trypanosomatidés, IRD (Institut de
Recherche pour le Développement), B.P. 64501, 911 avenue Agropolis, 34394
Montpellier Cédex 5, France. lemesre at mpl.ird.fr.

REFERENCE: Antimicrob Agents Chemother 2005 Oct 49(10):4406-9

We previously documented the induction of Leishmania amastigote 
apoptosis by trivalent antimony (SbIII) and nitric oxide (NO). We 
demonstrate here that SbIII-resistant amastigotes were resistant to NO 
toxicity when delivered extracellularly by NO donors or intracellularly 
via macrophage activation. Shared biochemical targets for SbIII and NO 
resistance in Leishmania are discussed.








PMID: 16023297
 

TITLE: Characterization of the redox components of transplasma membrane electron
transport system from Leishmania donovani promastigotes.

AUTHORS: Tanmoy Bera, Kuruba Lakshman, Debiprasad Ghanteswari, Sabita Pal,
Dharmalingam Sudhahar, Md Nurul Islam, Nihar Ranjan Bhuyan, Pradeep Das

AFFILIATION: Division of Medicinal Biochemistry, Department of Pharmaceutical
Technology, Jadavpur University, Kolkata-700032, India.

REFERENCE: Biochim Biophys Acta 2005 Oct 1725(3):314-26

An investigation has been made of the points of coupling of four 
nonpermeable electron acceptors e.g., alpha-lipoic acid (ALA), 5,5'-
dithiobis (2-nitroaniline-N-sulphonic acid) (DTNS), 1,2-naphthoquinone-4
-sulphonic acid (NQSA) and ferricyanide which are mainly reduced via an 
interaction with the redox sites present in the plasma membrane of 
Leishmania donovani promastigotes. ALA, DTNS, NQSA and ferricyanide 
reduction and part of O(2) reduction is shown to take place on the 
exoplasmic face of the cell, for it is affected by external pH and 
agents that react with the external surface. Redox enzymes of the 
transplasma membrane electron transport system orderly transfer electron
 from one redox carrier to the next with the molecular oxygen as the 
final electron acceptor. The redox carriers mediate the transfer of 
electrons from metabolically generated reductant to nonpermeable 
electron acceptors and oxygen. At a pH of 6.4, respiration of Leishmania
 cells on glucose substrate shut down almost completely upon addition of
 an uncoupler FCCP and K(+)-ionophore valinomycin. The most pronounced 
effects on O(2) uptake were obtained by treatment with antimycin A, 2-
heptadecyl-4-hydroxyquinone-N-oxide, paracholoromercuribenzene sulphonic
 acid and trifluoperazine. Relatively smaller effects were obtained by 
treatment with potassium cyanide. Inhibition observed with respect to 
the reduction of the electron acceptors ALA, DTNS, NQSA and ferricyanide
 was not similar in most cases. The redox chain appears to be branched 
at several points and it is suggested that this redox chain incorporate 
iron-sulphur center, b-cytochromes, cyanide insensitive oxygen redox 
site, Na(+) and K(+) channel, capsaicin inhibited energy coupling site 
and trifluoperazine inhibited energy linked P-type ATPase. We analyzed 
the influence of ionic composition of the medium on reduction of 
electron acceptors in Leishmania donovani promastigotes. Our data 
suggest that K(+) have some role for ALA reduction and Na(+) for 
ferricyanide reduction. No significant effects were found with DTNS and 
NQSA reduction when Na(+) or K(+) was omitted from the medium. 
Stimulation of ALA, DTNS, NQSA and ferricyanide reduction was obtained 
by omitting Cl(-) from the medium. We propose that this redox system may
 be an energy source for control of membrane function in Leishmania 
cells.




PMID: 16177338
 

TITLE: Antigen requirements for efficient priming of CD8+ T cells by leishmania
major-infected dendritic cells.

AUTHORS: Sylvie Bertholet, Alain Debrabant, Farhat Afrin, Elisabeth Caler,
Susana Mendez, Khaled S Tabbara, Yasmine Belkaid, David L Sacks

AFFILIATION: Laboratory of Parasitic Diseases, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,
USA.

REFERENCE: Infect Immun 2005 Oct 73(10):6620-8

CD4(+) and CD8(+) T-cell responses have been shown to be critical for 
the development and maintenance of acquired resistance to infections 
with the protozoan parasite Leishmania major. Monitoring the development
 of immunodominant or clonally restricted T-cell subsets in response to 
infection has been difficult, however, due to the paucity of known 
epitopes. We have analyzed the potential of L. major transgenic 
parasites, expressing the model antigen ovalbumin (OVA), to be presented
 by antigen-presenting cells to OVA-specific OT-II CD4(+) or OT-I CD8
(+) T cells. Truncated OVA was expressed in L. major as part of a 
secreted or nonsecreted chimeric protein with L. donovani 3' 
nucleotidase (NT-OVA). Dendritic cells (DC) but not macrophages infected
 with L. major that secreted NT-OVA could prime OT-I T cells to 
proliferate and release gamma interferon. A diminished T-cell response 
was observed when DC were infected with parasites expressing nonsecreted
 NT-OVA or with heat-killed parasites. Inoculation of mice with 
transgenic parasites elicited the proliferation of adoptively 
transferred OT-I T cells and their recruitment to the site of infection 
in the skin. Together, these results demonstrate the possibility of 
targeting heterologous antigens to specific cellular compartments in L. 
major and suggest that proteins secreted or released by L. major in 
infected DC are a major source of peptides for the generation of 
parasite-specific CD8(+) T cells. The ability of L. major transgenic 
parasites to activate OT-I CD8(+) T cells in vivo will permit the 
analysis of parasite-driven T-cell expansion, differentiation, and 
recruitment at the clonal level.




PMID: 16184230
 

TITLE: Phenotypic, functional, and quantitative characterization of canine
peripheral blood monocyte-derived macrophages.

AUTHORS: R Bueno, M N Mello, C A S Menezes, W O Dutra, R L Santos

AFFILIATION: Departamento de Clínica e Cirurgia Veterinárias, Escola de
Veterinária, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG,
31270-901, Brazil.

REFERENCE: Mem Inst Oswaldo Cruz 2005 Aug 100(5):521-4

The yield as well as phenotypic and functional parameters of canine 
peripheral blood monocyte-derived macrophages were analyzed. The cells 
that remained adherent to Teflon after 10 days of culture had high 
phagocytic activity when inoculated with Leishmania chagasi. Flow 
cytometric analysis demonstrated that more than 80% of cultured cells 
were positive for the monocyte/macrophage marker CD14.




********************************************************************************************************************

 The following references are revised files and are brought to you in accordance
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********************************************************************************************************************


PMID: 11867566
 

TITLE: The Trypanosoma cruzi trans-sialidase is a T cell-independent B cell
mitogen and an inducer of non-specific Ig secretion.

AUTHORS: Wenda Gao, Henry H Wortis, Miercio A Pereira

AFFILIATION: Parasitology Research Center, Department of Pathology, Tufts
University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.

REFERENCE: Int Immunol 2002 Mar 14(3):299-308

Polyclonal lymphocyte activation and hypergammaglobulinemia characterize
 the acute phase of many parasitic diseases, including Chagas' disease, 
a debilitating condition caused by Trypanosoma cruzi. Polyclonal 
lymphocyte activation correlates with disease susceptibility inT. cruzi 
infection. Thus, identifying factors that drive such reactivities should
 provide insight into mechanisms of parasite evasion from host immunity 
and of disease pathogenesis. Sensitization of mice with small doses of T
. cruzi trans-sialidase (TS) turns the mice into highly susceptible 
hosts to T. cruzi. In addition, TS heterologously expressed in 
Leishmania major greatly enhances virulence of the parasite to mice. In 
attempt to study the mechanism of TS-induced virulence, we found that TS
 and its C-terminal long tandem repeat (LTR) are T-independent 
polyclonal activators for mouse B cells. While B cells deficient/
defective in L-6, CD40 or Toll-like receptor-4 are similarly activated 
by TS as compared to wild-type cells, B cells from Bruton's tyrosine 
kinase-defective X-linked immunodeficient mice are remarkably 
insensitive to TS activation. TS-induced B cell activation in vitro is 
accompanied by Ig secretion independent of T cells. Furthermore, 
administration of TS into normal mice leads to non-specific Ig secretion
 that peaks 4-6 days after injection. Thus TS, through its LTR, induces 
abnormal polyclonal B cell activation and Ig secretion, which could 
explain in part its virulence-enhancing activity.




PMID: 11481434
 

TITLE: Trypanosoma cruzi trans-sialidase: a potent and specific survival factor
for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt
signaling.

AUTHORS: M V Chuenkova, F B Furnari, W K Cavenee, M A Pereira

AFFILIATION: Parasitology Research Center, Department of Pathology, Tufts
University School of Medicine, Boston, MA 02111, USA.

REFERENCE: Proc Natl Acad Sci U S A 2001 Aug 98(17):9936-41

Patients infected with Trypanosoma cruzi may remain asymptomatic for 
decades and show signs of neuroregeneration in the peripheral nervous 
system (PNS). In the absence of such neuroregeneration, patients may die
 in part by extensive neuronal destruction in the gastrointestinal tract
. Thus, T. cruzi may, despite their invasion of the PNS, directly 
prevent cell death to keep nerve destruction in check. Indeed, T. cruzi 
invasion of Schwann cells, their prime target in PNS, suppressed host-
cell apoptosis caused by growth-factor deprivation. The trans-sialidase
 (TS) of T. cruzi and the Cys-rich domain of TS reproduced the 
antiapoptotic activity of the parasites at doses (> or =3.0 nM) 
comparable or lower than those of bona fide mammalian growth factors. 
This effect was blocked by LY294002, an inhibitor of 
phosphatidylinositol 3-kinase (PI3K). TS also activated Akt, a 
downstream effector of PI3K. Ectopic expression of TS in an unrelated 
parasite, Leishmania major, turned those parasites into activators of 
Akt in Schwann cells. In contrast, the Cys-rich domain of TS did not 
block apoptosis in Schwann cells overexpressing dominant-negative Akt or
 constitutively active PTEN, a negative regulator of PI3K/Akt signaling
. The results demonstrate that T. cruzi, through its TS, triggers the 
survival of host Schwann cells via the PI3K/Akt pathway, suggesting a 
role for PI3K/Akt in the pathogenesis of Chagas' disease.




PMID: 7676903
 

TITLE: Distribution of developmentally regulated trans-sialidases in the
Kinetoplastida and characterization of a shed trans-sialidase activity from
procyclic Trypanosoma congolense.

AUTHORS: M Engstler, R Schauer, R Brun

AFFILIATION: Biochemisches Institut, Christian-Albrechts-Universität, Kiel,
FRG.

REFERENCE: Acta Trop 1995 May 59(2):117-29

The expression of developmentally regulated sialidase and trans-
sialidase activities in kinetoplastid protozoa was investigated. The 
occurrence of these enzymes was found not to be a common feature among 
the Kinetoplastida, but to be restricted to distinct developmental life 
cycle stages of only a few species. While sialidases without trans-
sialylating activities were demonstrated in Trypanosoma vivax and T. 
rangeli, trans-sialidase activity is expressed throughout the brucei-
group and in T. congolense. Neither T. evansi, nor T. equiperdum express
 sialidases or trans-sialidases. Furthermore, the absence of both, 
sialidase and trans-sialidase activities was proven in the Leishmania, 
Crithidia, Herpetomonas, Leptomonas and Phytomonas, respectively. In all
 species tested, the occurrence of sialic acids coincides with the 
expression of trans-sialidase activity. Those parasites, which lack 
trans-sialidases or only display regular sialidases, also lack cell-
bound sialic acids. The regular sialidase activity from bloodstream form
 T. vivax was characterized. The trans-sialidase from T. congolense is 
restricted to the procyclic culture forms and is shed into the culture 
medium. The enzyme has a pH-optimum at pH 7.0, displays sensitivity 
towards chlorides and is resistant against commonly used sialidase 
inhibitors. T. congolense trans-sialidase transfers preferentially alpha
(2-3)-linked sialic acids onto terminal beta-galactose residues. Also 
hydroxylated sialic acids (Neu5Gc) are transferred. The major 
glycoprotein GARP from procyclic T. congolense was identified as one 
potential natural sialic acid acceptor on the parasite's surface. In 
order to facilitate the characterization of trans-sialidases a novel, 
fluorimetric trans-sialidase assay was developed.




PMID: 7935605
 

TITLE: Combined occurrence of trypanosomal sialidase/trans-sialidase activities
and leishmanial metalloproteinase gene homologues in Endotrypanum sp.

AUTHORS: E Medina-Acosta, S Paul, S Tomlinson, L C Pontes-de-Carvalho

AFFILIATION: Rockefeller University, New York, NY.

REFERENCE: Mol Biochem Parasitol 1994 Apr 64(2):273-82

Endotrypanum (order Kinetoplastida: family Trypanosomatidae) is a 
parasite of forest dwelling tree sloths (Edentata: genera Choleopus and 
Bradypus). Unique among the haemoflagellates, this protozoan has an 
intraerythrocytic phase in the mammalian host. Nevertheless, many 
striking similarities exist between Endotrypanum and the human pathogen 
Leishmania that make it a useful model for epidemiological and 
evolutionary aspects of the biology of trypanosomatids. Importantly, 
Endotrypanum species share both the insect vector and host reservoir 
with certain species of Leishmania (subgenus Viannia). Because mixed 
infections with Endotrypanum and Leishmania are common in sloths and, 
therefore, likely to occur in the sandfly vector, there is a need for 
adequate biochemical markers to distinguish Endotrypanum from Leishmania
 infections. In this paper we show that Endotrypanum promastigotes 
possess sialidase and trans-sialidase activities, which are absent from 
Leishmania, and which are not closely related to the previously 
described trypanosomal sialidase/trans-sialidase enzyme. We also 
document the occurrence in Endotrypanum of homologues of the leishmanial
 surface metalloproteinase gp63 genes. The combined occurrence of 
sialidase/trans-sialidase activities and gp63 gene homologues in a 
unique organism has important ramifications for both field and 
laboratory studies on the biology of trypanosomatids, especially those 
related to host infection and evolution.




PMID: 7033434
 

TITLE: Receptor for immunoglobulin Fc on pathogenic but not on nonpathogenic
protozoa of the Trypanosomatidae.

AUTHORS: I K De Miranda-Santos, A Campos-Neto

REFERENCE: J Exp Med 1981 Dec 154(6):1732-42

Members of the Trypanosomatidae were studied for their ability to 
acquire host IgG through a possible Fc receptor. A simple rosette test 
was devised in which the different species and forms of protozoa were 
mixed with SRBC sensitized with subagglutinating does of IgG, IgM, and F
 (ab') 2 anti-SRBC, and the pelleted mixture was observed for the number
 of clumps (rosettes) formed between the parasites and SRBC. Rosettes 
were formed between parasites and SRBC sensitized with IgG but not with 
IgM or F(ab')2, indicating the presence of a receptor for IgG Fc. The 
specificity of this receptor for Fc was confirmed by inhibition 
experiments with normal rabbit aggregated gammaglobulins or with 
purified normal rabbit Fc. The receptor is sensitive to treatment with 
trypsin but regenerates after a short period of incubation (1 h), which 
indicates that it is synthesized by the parasite itself. Interesting was
 the observation that only pathogenic members of the Trypanosomatidae 
formed rosettes with sensitized SRBC. In none of the nonpathogenic forms
 studied could we demonstrate the Fc receptor. Also important was the 
finding that freshly isolated blood stream forms of Trypanosoma cruzi 
from infected mice did not form rosettes. However, after trypsinization
, these forms clearly displayed the ability to do so, possibly 
indicating a previous acquisition of the host IgG by the parasites in 
the mouse blood stream. These findings point to a possible and important
 means of parasite evasion of the host immune response by masking their 
surface with host IgG.




REQUEST: [ sand fly ]

(0 articles match this request)



REQUEST: [ sandfly ]

(1 article matches this request. 1 article matching other requests removed)














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