[leish-l] Fwd: Articles found by RefScout 205/09/28 - 2005/39
jeffreyj at usp.br
jeffreyj at usp.br
Fri Oct 7 18:40:09 BRT 2005
Date: Wed, 28 Sep 2005 04:56:15
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This is RefScout-Newsletter 39/2005.
REQUEST: [ leishmaniasis ]
(13 articles match this request)
PMID: 16178911
TITLE: Infection-associated haemophagocytosis: the tropical spectrum.
AUTHORS: Z N Singh, D Rakheja, T P Yadav, D K Shome
AFFILIATION: Department of Pathology, Maulana Azad Medical College, New Delhi,
India.
REFERENCE: Clin Lab Haematol 2005 Oct 27(5):312-5
Summary Reactive proliferation and inappropriate activation of mature
histiocytes with haemophagocytosis (HP) may occur in association with a
wide variety of infections, neoplasms, collagen vascular diseases, and
acquired and inherited immunodeficiency states. The association with
infections is particularly important because overwhelming HP can obscure
the typical clinical features of the primary disease and negatively
affects outcome. A high index of suspicion is required for early
recognition of associated HP as the cause of cytopenias. Institution of
specific therapy is crucial for survival. This study highlights the wide
spectrum of tropical diseases that can have associated reactive HP.
Thirty cases with documented prominent HP on bone marrow aspiration
smears were reviewed. Twenty-one (69%) of the marrows were from patients
who had common tropical infections: malaria, typhoid and visceral
leishmaniasis and 11 of 15 patients (73%) who were followed up improved
on specific infection-directed and supportive measures. The presence of
severe HP in bone marrow smears correlated with marked cytopenias.
Recognition of HP in this geographical region should stimulate the
search for one of these infections as early institution of specific
therapy is crucial for patient survival.
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, CHUQ,
2705 Laurier Blvd., Quebec (QC), Canada G1V 4G2.
barbara.papadopoulou at crchul.ulaval.ca.
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: Department of Dermatology, Charité University Medicine Berlin,
Humboldt University, Schumannstr. 20/21, D-10117 Berlin, Germany.
peter.walden at charite.de.
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.
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: 16028140
TITLE: Fms-like tyrosine kinase 3-based immunoprophylaxis against infection is
improved by adjuvant treatment with anti-interleukin-10 antibody.
AUTHORS: Lopamudra Das, Jennifer DeVecchio, Frederick P Heinzel
AFFILIATION: Center for Global Health and Diseases and Department of Medicine,
Case Western Reserve University, Cleveland, Ohio 44106-7286, USA.
REFERENCE: J Infect Dis 2005 Aug 192(4):693-702
BACKGROUND. Fms-like tyrosine kinase 3 ligand (Flt3L) expands dendritic-
cell populations in vivo and protects against microbial infection in
healthy and immunocompromised hosts. Approaches for optimizing the
protective effects of Flt3L in vivo are not well known.METHODS. BALB/c
mice were treated for 9 days with 10 microg of recombinant (r) Flt3L
with or without the addition of 250 microg of anti--interleukin (IL)-10
antibody on day 9. After Leishmania major infection, disease progression
was determined by measuring cutaneous lesions. Production of IL-12 and
interferon (IFN)- gamma were determined.RESULTS. Flt3L pretreatment
increased the synthesis of CD40-inducible IL-12 p40 but not of bioactive
p70. Coculture with anti--IL-10 antibody increased p70 production.
Combined Flt3L and single-dose anti--IL-10 antibody pretreatment
improved lesion cure rates from 40% to 87% relative to mice pretreated
with rFlt3L only (P<.01, chi (2) test) and increased T helper 1 (Th1
)--type cytokine production 4 weeks after infection but did not cure Rag
-2-- and IFN- gamma -knockout BALB/c mice. Flt3L and anti-IL-10 antibody
pretreatments increased frequencies of IL-12- and IFN- gamma -secreting
cells 2 and 4 days after infection. Both natural killer and CD4(+)
cells contributed to increased early IFN- gamma production.CONCLUSION. A
single dose of anti--IL-10 antibody significantly improves Flt3L
immunoprophylaxis against infection mediated by Th1-type adaptive
responses.
PMID: 15955815
TITLE: Down-regulation of 7SL RNA expression and impairment of vesicular protein
transport pathways by Leishmania infection of macrophages.
AUTHORS: Smita Misra, Manish K Tripathi, Gautam Chaudhuri
AFFILIATION: Division of Microbial Pathogenesis and Immune Response, Department
of Biomedical Sciences, Meharry Medical College, Nashville, TN 37208, USA.
REFERENCE: J Biol Chem 2005 Aug 280(32):29364-73
The parasitic protozoan Leishmania specifically manipulates the
expression of host macrophage genes during initial interactions, as
revealed by mRNA differential display reverse transcription-PCR and cDNA
microarray analyses. The genes that are down-regulated in mouse (J774G8
) or human (U937) macrophages upon exposure to Leishmania include small
RNA transcripts from the short interspersed element sequences. Among the
short interspersed element RNAs that are down-regulated is 7SL RNA,
which is the RNA component of the signal recognition particle. Because
the microbicidal functions of macrophages profoundly count on vesicular
protein transport processes, down-regulation of 7SL RNA may be
significant in the establishment of infection by Leishmania in
macrophage phagolysosomes. To evaluate whether down-regulation of 7SL
RNA results in inhibition of signal recognition particle-mediated
vesicular protein transport processes, we have tested and found that the
targeting of proteins to the endoplasmic reticulum and plasma membrane
and the secretion of proteins by macrophages are compromised in
Leishmania-infected J774G8 and U937 cells. Knocking down 7SL RNA using
small interfering RNA mimicked the effect of exposure of macrophages to
Leishmania. The overexpression of 7SL RNA in J774G8 or U937 cells made
these cells resistant to Leishmania infection, suggesting the possible
biological significance of down-regulation of 7SL RNA synthesis in the
establishment of infection by Leishmania. We conclude that Leishmania
down-regulates 7SL RNA in macrophages to manipulate the targeting of
many proteins that use the vesicular transport pathway and thus favors
its successful establishment of infection in macrophages.
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 Ep Corbett
AFFILIATION: Departamento de Parasitologia, Instituto Evandro Chagas, Belém,
PA, 66090-000, Brasil.
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: 16175986
TITLE: Mucocutaneous leishmaniasis presenting as facial cellulitis.
AUTHORS: Rima Clayton, Sophie Grabczynska
AFFILIATION: Amersham Hospital, Whielden Street, Amersham, Buckinghamshire, UK.
r.clayton at doctors.org.uk
REFERENCE: J Laryngol Otol 2005 Jul 119(7):567-9
We report a case of mucocutaneous leishmaniasis caused by Leishmania
viannia braziliensis. Despite several courses of both oral and
intravenous antibiotics no improvement was seen. This case highlights
the importance of taking a thorough history, including details of recent
travel, and considering rarer causes when no improvement with
antibiotics is seen. Our patient was infected with a particularly
virulent strain and destruction of the mucous membranes is not uncommon
. Rapid diagnosis and treatment are therefore crucial.
PMID: 15378355
TITLE: Complement C3 is required for the progression of cutaneous lesions and
neutrophil attraction in Leishmania major infection.
AUTHORS: Thomas Jacobs, Jörg Andrä, Iris Gaworski, Sebastian Graefe, Katja
Mellenthin, Manfred Krömer, Roman Halter, Jürgen Borlak, Joachim Clos
AFFILIATION: Department of Immunology, Bernhard Nocht Institute for Tropical
Medicine, Bernhard-Nocht-Str. 74, 20359, Hamburg, Germany.
tjacobs at bni-hamburg.de
REFERENCE: Med Microbiol Immunol (Berl) 2005 May 194(3):143-9
To elucidate the role of complement-mediated uptake in Leishmania major
infection in vivo, transgenic BALB/c mice that express the cobra venom
factor (CVF) under control of the alpha1-antitrypsin promoter were
infected. CVF expression in these mice leads to a continuous activation
and subsequent consumption of complement C3 in the serum. In contrast to
susceptible non-transgenic BALB/c mice, CVF-transgenic mice are highly
resistant to L. major infection and show a significantly reduced
parasite dissemination. Transient depletion of C3 in wild-type BALB/c
mice delays progression of lesions for some days. Both CVF-transgenic
and non-transgenic mice exhibit similar T cell responses upon infection
. However, in CVF-transgenic mice, no infiltration of neutrophils, which
were the prominent infiltrating cells at the site of infection in
normal susceptible mice, could be detected. We conclude that C3 cleavage
is required for the attraction of neutrophils that participate in
parasite dissemination.
PMID: 16172767
TITLE: [Antimonial treatments of leishmaniasis.]
AUTHORS: Manoel Paes de Oliveira Neto
AFFILIATION: Ambulatório de Leishmaniose do Serviço de Especialidades
ClÃnicas, Departamento de Doenças Infecciosas, Instituto de Pesquisa ClÃnica
Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
REFERENCE: Rev Soc Bras Med Trop 2005 Sep-Oct 38(5):446
PMID: 16172760
TITLE: [Aspects of the ecology and behaviour of phlebotomines in endemic area
for visceral leishmaniasis in State of Minas Gerais.]
AUTHORS: Ricardo Andrade Barata, João Carlos França-Silva, Wilson Mayrink,
Jaime Costa da Silva, AluÃzio Prata, Elias Seixas Lorosa, Jaqueline Araújo
Fiúza, Caroline Macedo Gonçalves, Kênia Maria de Paula, Edelberto Santos
Dias
AFFILIATION: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo
Horizonte, MG.
REFERENCE: Rev Soc Bras Med Trop 2005 Sep-Oct 38(5):421-5
Studies on the behavioral and feeding habits of some species of
phlebotominae sand flies have contributed to the comprehension of the
epidemiology of leishmaniasis. In the present work, systematic captures
were performed monthly in the municipality of Porteirinha (MG) using 28
light traps (CDC) from January to December 2002. Fourteen different
species of phlebotomine were captured in a total of 1,408 specimens. The
highest percentage of individuals (53.3%) was collected in the
peridomicile against 46.7% in the intradomicile. Lutzomyia longipalpis
was the predominant species in that region. The blood feeding of 38
females of this species from the field was analyzed by precipitin
reaction. The results indicated that Lutzomyia longipalpis is an
opportunist (65.1%) species that feeds on a wide variety of vertebrates
in nature.
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-MartÃnez, M Campillo, I L
Bazzocchi, L Pardo, A G Ravelo, S Castanys, F Gamarro
AFFILIATION: Instituto de ParasitologÃa y Biomedicina "López-Neyra", Consejo
Superior de Investigaciones CientÃficas, Parque Tecnológico de Ciencias de la
Salud, Avda. del Conocimiento s/n, 18100-Armilla, Granada, Spain.
gamarro at ipb.csic.es.
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: 16182864
TITLE: Genes and susceptibility to leishmaniasis.
AUTHORS: Emanuela Handman, Colleen Elso, Simon Foote
AFFILIATION: The Walter and Eliza Hall Institute of Medical Research, Post
Office, Royal Melbourne Hospital, Victoria 3050, Australia.
REFERENCE: Adv Parasitol 2005 59():1-75
Leishmania are digenetic protozoa which inhabit two highly specific
hosts, the sandfly where they grow as motile, flagellated promastigotes
in the gut, and the mammalian macrophage where they grow intracellularly
as non-flagellated amastigotes. Leishmaniasis is the outcome of an
evolutionary 'arms race' between the host's immune system and the
parasite's evasion mechanisms which ensure survival and transmission in
the population. The spectrum of disease manifestations and severity
reflects the interaction between the genome of the host and that of the
parasite, and the pathology is caused by a combination of host and
parasite molecules. This chapter examines the genetic basis of host
susceptibility to disease in humans and animal models. It describes the
genetic tools used to map and identify susceptibility genes, and the
lessons learned from murine and human cutaneous leishmaniasis.
REQUEST: [ leishmania ]
(19 articles match this request. 7 articles matching other requests removed)
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, NIAID, Bldg. 4, Room 126, 4
Center Dr., MSC 0425, Bethesda, MD 20892-0425. dsacks at nih.gov.
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: 16141242
TITLE: Genetic background influences immune responses and disease outcome of
cutaneous L. mexicana infection in mice.
AUTHORS: Lucia E Rosas, Tracy Keiser, Joseph Barbi, Anjali A Satoskar, Alecia
Septer, Jennifer Kaczmarek, Claudio M Lezama-Davila, Abhay R Satoskar
AFFILIATION: Department of Microbiology.
REFERENCE: Int Immunol 2005 Oct 17(10):1347-57
The experimental model of high-dose Leishmania mexicana infection is
used frequently to study molecular mechanisms regulating T(h)2 response
since most inbred mice regardless of their genetic background display T(
h)2 cytokine-dependent susceptibility to L. mexicana unlike Leishmania
major. Here, we analyzed the course of L. mexicana infection in BALB/c,
C57BL/6 and CBA/J mouse strains using low-dose ear infection model that
mimics natural transmission. Although all three strains were equally
susceptible to high-dose back rump L. mexicana infection, they displayed
marked differences in their ability to control parasite growth after
low-dose ear infection. Leishmania mexicana-infected BALB/c mice
produced high levels of T(h)2-associated cytokines and developed non-
healing lesions full of parasites, whereas CBA/J mice preferentially
produced T(h)1-associated IFN-gamma but low levels of IL-4, and
developed small self-resolving lesions. Both BALB/c and C57BL/6 mice
produced comparable amounts of IFN-gamma following L. mexicana infection
, but later produced less T(h)2-associated cytokines, and exhibited an '
intermediate' susceptibility phenotype characterized by lesion sizes
that were significantly smaller than BALB/c mice but larger than CBA/J
mice. Interestingly, all three strains also showed marked differences in
trafficking of macrophages, CD4+ T cells and CD8+ T cells into their
lesions. Finally, we analyzed the course of low-dose L. mexicana
infection in signal transducers and activators of transcription (STAT) 6
-/- and STAT6+/+ BALB/c mice. We found that STAT6-/- mice mount a T(h)1
response, produce high levels of IL-12 and IFN-gamma and develop smaller
lesions containing fewer parasites as compared with STAT6+/+ mice. Our
findings demonstrate that genetic background plays a critical role in
determining susceptibility of inbred mice to low-dose L. mexicana
infection. Furthermore, together with our previous findings, they show
that STAT6-mediated signaling is involved in mediating susceptibility to
L. mexicana following both high-dose back rump and low-dose ear dermis
infection.
PMID: 16179733
TITLE: Murine macrophages produce endothelin-1 after microbial stimulation.
AUTHORS: Jeffrey R Wahl, Nicholas J Goetsch, Heather J Young, Ryan J Van Maanen,
Jason D Johnson, Anisa S Pea, Andrew Brittingham
AFFILIATION: Department of Microbiology, Des Moines University, College of
Osteopathic Medicine, 3200 Grand Avenue, Des Moines, Iowa 50312.
Andrew.Brittingham at dmu.edu.
REFERENCE: Exp Biol Med (Maywood) 2005 Oct 230(9):652-8
Endothelin-1 (ET-1) was originally characterized as a potent
vasoconstrictor secreted by the endothelium and participating in the
regulation of vascular tone. Subsequent analysis has revealed ET-1 to be
a multifunctional peptide produced by a wide variety of cells and
tissues under normal and pathologic conditions. The importance of
macrophages as a source of ET-1 during infection and inflammation is
supported by clinical observations in humans and in animal models of
inflammation. We hypothesize that the production of ET-1 is part of the
characteristic macrophage response to infection, and have begun to
investigate the ability of various classes of microbes or microbial
products to induce macrophage ET-1 production. We report the production
of ET-1 by murine macrophages in response to stimulation with both gram-
positive and gram-negative bacteria. Stimulation of macrophages with
yeast (Candida albicans or Saccharomyces cerevisiae) or the protozoan
parasite Leishmania major, elicited no significant release of ET-1. The
production of ET-1 in response to lipopolysaccharide (LPS) was dose and
time dependent, and required the expression of a functional toll-like
receptor 4 (TLR4). Pharmacologic inhibition of the transcription factor
, nuclear factor-kappaB (NF-kappaB) suppressed LPS-induced ET-1
production. Our findings complement the growing body of literature
implicating a role for macrophage-derived ET-1 in inflammatory
pathologies. The production of ET-1 by macrophages during infection and
inflammation has the potential to affect tissue perfusion, leukocyte
extravasation, and immune cell function.
PMID: 15929724
TITLE: Peroxin 5-peroxin 14 association in the protozoan Leishmania donovani
involves a novel protein-protein interaction motif.
AUTHORS: Kleber P Madrid, Armando Jardim
AFFILIATION: Institute of Parasitology, McGill University, Macdonald Campus,
Ste. Anne de Bellevue, Quebec, Canada H9X 3V9.
REFERENCE: Biochem J 2005 Oct 391(Pt 1):105-14
Import of proteins with a PTS1 (peroxisomal targeting signal 1) into the
Leishmania glycosomal organelle involves docking of a PTS1-laden LdPEX5
[Leishmania donovani PEX5 (peroxin 5)] receptor to LdPEX14 on the
surface of the glycosomal membrane. In higher eukaryotes, the PEX5-PEX14
interaction is mediated by a conserved diaromatic WXXXY/F motif. Site-
directed and deletion mutageneses of the three WXXXY/F repeats in LdPEX5
did not abolish the LdPEX5-LdPEX14 association. Analysis of the
equilibrium dissociation constant (K(d)) revealed that ldpex5-W53A (
Trp53-->Ala), ldpex5-W293A, ldpex5-W176,293A and ldpex5-W53,176,293A
mutant receptors were capable of binding LdPEX14 with affinities
comparable with wild-type LdPEX5. That the diaromatic motifs were not
required for the LdPEX5-LdPEX14 interaction was further verified by
deletion analysis that showed that ldpex5 deletion mutants or ldpex5
fragments lacking the WXXXY/F motifs retained LdPEX14 binding activity.
Mapping studies of LdPEX5 indicated that the necessary elements required
for LdPEX14 association were localized to a region between residues 290
and 323. Finally, mutational analysis of LdPEX14 confirmed that
residues 23-63, which encompass the conserved signature sequence
AX2FLX7SPX6FLKGKGL/V present in all PEX14 proteins, are essential for
LdPEX5 binding.
PMID: 16174412
TITLE: Germ-free mice produce high levels of interferon-gamma in response to
infection with Leishmania major but fail to heal lesions.
AUTHORS: M R Oliveira, W L Tafuri, L C C Afonso, M A P Oliveira, J R Nicoli, E C
Vieira, P Scott, M N Melo, L Q Vieira
AFFILIATION: Departamento de Parasitologia, ICB, Universidade Federal de Minas
Gerais, CP486, 30161-970, Belo Horizonte, MG, BrazilDepartamento de Biologia
Molecular, CCEN, Universidade Federal da ParaÃba, Campus I. 58059-900, João
Pessoa, PB, Brazil.
REFERENCE: Parasitology 2005 Oct 131(Pt 4):477-88
In order to investigate the importance of the host microbiota on
differentiation of T cell subsets in response to infection, Swiss/NIH
germ-free mice and conventional (microbiota-bearing) mice were infected
with Leishmania major , and lesion development, parasite loads, and
cytokine production were assessed. Germ-free mice failed to heal lesions
and presented a higher number of parasites at the site of infection
than their conventional counterparts. In addition, histopathological
analysis indicated a higher density of parasitized macrophages in
lesions from germ-free mice than in conventional mice. The initial
production of interleukin (IL)-12 and interferon-gamma (IFN-gamma) in
germ-free mice was comparable to the conventional controls. Also, germ-
free mice produced elevated levels of IFN-gamma and lower levels of IL-4
throughout the course of infection, suggesting the development of a Th1
response. Macrophages from germ-free mice exposed to IFN-gamma and
infected with amastigotes in vitro were not as efficient at killing
parasites as macrophages from conventional animals. These observations
indicate that the microbiota is not essential for the development of Th1
immune responses, but seems to be important for macrophage activation.
PMID: 16145753
TITLE: A feast of protozoan genomes.
AUTHORS: Christiane Hertz-Fowler, Matthew Berriman, Arnab Pain
REFERENCE: Nat Rev Microbiol 2005 Sep 3(9):670-1
PMID: 16178353
TITLE: Differential polyadenylation of ribosomal RNA during post-transcriptional
processing in Leishmania.
AUTHORS: S Decuypere, J Vandesompele, V Yardley, S De Donckeri, T Laurent, S
Rijal, A Llanos-Cuentas, F Chappuis, J Arevalo, J C Dujardin
AFFILIATION: Department of Parasitology, Unit of Molecular Parasitology, Prince
Leopold Institute of Tropical Medicine, Antwerp B-2000, Belgium.
REFERENCE: Parasitology 2005 Sep 131(Pt 3):321-9
The protozoan parasite Leishmania belongs to the most ancient eukaryotic
lineages and this is reflected in several distinctive biological
features, such as eukaryotic polycistronic transcription and RNA trans-
splicing. The disclosure of this organism's unusual characteristics
leads to a better understanding of the origin and nature of fundamental
biological processes in eukaryotes. Here we report another unusual
phenomenon as we demonstrate that precursor ribosomal RNA can be
extensively polyadenylated during post-transcriptional processingt.
Furthermore, we demonstrate that the degree of precursor rRNA
polyadenylation is variable in different strains and in the different
life-stages of a strain.
PMID: 16178423
TITLE: Identification of the +1 ribosomal frameshifting site of LRV1-4 by
mutational analysis.
AUTHORS: Se Na Kim, Jung Ho Choi, Min Woo Park, Sun Joo Jeong, Kyung Sook Han,
Hong Jin Kim
AFFILIATION: College of Pharmacy, Chung Ang University, 221 Huksuk-Dong,
Dongjak-Ku, Seoul 156-756, Korea.
REFERENCE: Arch Pharm Res 2005 Aug 28(8):956-62
Leishmania virus (LRV)1-4 has been reported to produce a fusion of ORF2
and ORF3 via a programmed +1 frameshift in the region where ORF2 and
ORF3 overlap (Lee et al., 1996). However, the exact frameshift site has
not been identified. In this study, we compared the frameshift
efficiency of a 259bp (nt. 2565-2823), frameshift region of LRV1-4, and
the 71bp (nt. 2605-2678) sub-region where ORF2 and ORF3 overlap. We then
predicted the frameshift site using a new computer program (
Pseudoviewer), and finally identified the specific region associated
with the mechanism of the LRV1-4's +1 frameshift by means of a
mutational analysis based on the predicted structure of LRV1-4 RNA. The
predicted structure was confirmed by biochemical analysis. In order to
measure the frameshift efficiency, constructs that generate luciferase
without a frameshift or with a +1 frameshift, were generated and in
vitro transcription/translation analysis was performed. Measurements of
the luciferase activity generated, showed that the frameshift efficiency
was about 1% for both the 259bp (LRV1-4 259FS) and 71bp region (LRV1-4
71FS). Luciferase activity was strongly reduced in a mutant (LRV1-4 NH:
nt. 2635-2670) with the entire hairpin deleted and in a mutant (LRV1-4
NUS: nt. 2644-2659) with the upper stem of the hairpin deleted. These
results indicate that the frameshift site in LRV1-4's is in the 71bp
region where ORF2 and ORF3 overlap, and that nt. 2644-2659 (the upward
hairpin stem) play a key role in generating the +1 frameshift.
PMID: 16184230
TITLE: Phenotypic, functional, and quantitative characterization of canine
peripheral blood monocyte-derived macrophages.
AUTHORS: R Bueno, Mn Mello, Cas Menezes, Wo Dutra, Rl Santos
AFFILIATION: Departamento de ClÃnica e Cirurgia Veterinárias, Escola de
Veterinária, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG,
31270-901, Brasil.
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.
PMID: 16044686
TITLE: Remote Sensing and Geographic Information Systems and risk of American
visceral leishmaniasis in Bahia, Brazil.
AUTHORS: M E Bavia, D D Madureira Trabuco Carneiro, H da Costa Gurgel, C
Madureira Filho, M G Rodrigues Barbosa
AFFILIATION: Universidade Federal da Bahia, Brasil. newmeb2004 at yahoo.com.br
REFERENCE: Parassitologia 2005 Mar 47(1):165-9
The spatial distribution of American visceral leishmaniasis (VL) was
studied within the context of the environmental characteristics of
northwest Bahia State in Brazil during an epidemic year. Geographic
Information Systems (GIS) and Remote Sensing (RS) were used to
characterize the landscape epidemiology of VL in order to identify and
map high risk areas and endemic zones in a northwestern Bahia study area
. Normalized Difference Vegetation Index (NDVI) was shown to be one of
the most important risk factors in the area of study. Low NDVI values
were related to high numbers of sand flies and high numbers of human and
canine VL positive cases. Caatinga vegetation type was the dominant
vegetation type in the endemic area. The use of RS and GIS allowed the
identification of classes of VL risk that may be useful information to
guide control program interventions.
PMID: 16170905
TITLE: Macrophage and Leishmania: an unacceptable coexistence.
AUTHORS: Mukul Kumar Basu, Mitali Ray
AFFILIATION: Biomembrane Division, Indian Institute of Chemical Biology,
Calcutta, India. mukulkbasu at yahoo.com
REFERENCE: Crit Rev Microbiol 2005 31(3):145-54
Research over the past year has revealed several significant and
interesting advances in the biology of macrophage, key cells responsible
in body's host defense against invading pathogens and in immune
responses. Perturbation of macrophage surface with different bacterial
pathogens leads to activate general signal transduction pathways of
macrophages, including activation of NADPH oxidase, nitric oxide
synthase, and so on. However, in this review, the results of macrophage
interactions only with Leishmania parasites, which harbors the host
macrophages, are discussed. It appears that interference in transduction
of regulatory signals during leishmanial invasion lead to an inadequate
leishmanicidal response. In this connection, information concerning
regulation of MHC molecules and other current events related to
macrophage function after invasion by the parasites are also discussed.
********************************************************************************************************************
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PMID: 10942757
TITLE: Isolation and characterization of gomesin, an 18-residue cysteine-rich
defense peptide from the spider Acanthoscurria gomesiana hemocytes with
sequence similarities to horseshoe crab antimicrobial peptides of the
tachyplesin family.
AUTHORS: P I Silva, S Daffre, P Bulet
AFFILIATION: Laboratório de Artrópodes, Instituto Butantan, Avenue Vital
Brazil, 1500, CEP 05503-900, São Paulo, Brazil.
REFERENCE: J Biol Chem 2000 Oct 275(43):33464-70
We have purified a small size antimicrobial peptide, named gomesin, from
the hemocytes of the unchallenged tarantula spider Acanthoscurria
gomesiana. Gomesin has a molecular mass of 2270.4 Da, with 18 amino
acids, including a pyroglutamic acid as the N terminus, a C-terminal
arginine alpha-amide, and four cysteine residues forming two disulfide
bridges. This peptide shows marked sequence similarities to
antimicrobial peptides from other arthropods such as tachyplesin and
polyphemusin from horseshoe crabs and androctonin from scorpions.
Interestingly, it also shows sequence similarities to protegrins,
antimicrobial peptides from porcine leukocytes. Gomesin strongly affects
bacterial growth, as well as the development of filamentous fungi and
yeast. In addition, we showed that gomesin affects the viability of the
parasite Leishmania amazonensis.
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