[leish-l] Fwd: Articles found by RefScout 06/04/2005 - 14/2005
jeffreyj at usp.br
jeffreyj at usp.br
Wed Apr 6 21:27:42 BRT 2005
Jeffrey J. Shaw Ph.D., D.Sc., OBE.,
Professor Titular, Vice-Chefe do Departmento,
Gerente "International Leishmania Network©",
Departmento de Parasitologia,
Instituto de Ciências Biomédicas,
Universidade de São Paulo (USP),
Av. Prof. Lineu Prestes, 1374,
05508-900 São Paulo, Brazil.
Telefone: 55-11-3091-7633 or 55-11-9732-2954
Fax: 55-11-3091-7417
Email: jeffreyj at usp.br
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This is RefScout-Newsletter 14/2005
REQUEST: [ leishmaniasis ]
(12 articles match this request)
PMID: 15804578
TITLE: Melanogenesis and associated cytotoxic reactions: Applications to insect
innate immunity.
AUTHORS: A J Nappi, B M Christensen
AFFILIATION: Department of Animal Health and Biomedical Sciences, University of
Wisconsin-Madison, 1556 Linden Drive, Madison, WI 53706, USA.
REFERENCE: Insect Biochem Mol Biol 2005 May 35(5):443-59
Insects transmit the causative agents for such debilitating diseases as
malaria, lymphatic filariases, sleeping sickness, Chagas' disease,
leishmaniasis, river blindness, Dengue, and yellow fever. The
persistence of these diseases provides testimony to the genetic capacity
of parasites to evolve strategies that ensure their successful
development in two genetically diverse host species: insects and mammals
. Current efforts to address the problems posed by insect-borne diseases
benefit from a growing understanding of insect and mammalian immunity.
Of considerable interest are recent genomic investigations that show
several similarities in the innate immune effector responses and
associated regulatory mechanisms manifested by insects and mammals. One
notable exception, however, is the nearly universal presence of a brown-
black pigment accompanying cellular innate immunity in insects. This
response, which is unique to arthropods and certain other invertebrates
, has focused attention on the elements involved in pigment synthesis as
causing or contributing to the death of the parasite, and has even
prompted speculation that the enzyme cascade mediating melanogenesis
constitutes an ill-defined recognition mechanism. Experimental evidence
defining the role of melanin and its precursors in insect innate
immunity is severely lacking. A great deal of what is known about
melanogenesis comes from studies of the process occurring in mammalian
systems, where the pigment is synthesized by such diverse cells as those
comprising portions of the skin, hair, inner ear, brain, and retinal
epithelium. Fortunately, many of the components in the metabolic
pathways leading to the formation of melanin have been found to be
common to both insects and mammals. This review examines some of the
factors that influence enzyme-mediated melanogenic responses, and how
these responses likely contribute to blood cell-mediated, target-
specific cytotoxicity in immune challenged insects.
PMID: 15796747
TITLE: Genetic variation in the sand fly salivary protein, SP-15, a potential
vaccine candidate against Leishmania major.
AUTHORS: D-E A Elnaiem, C Meneses, M Slotman, G C Lanzaro
AFFILIATION: Department of Entomology, University of California at Davis, Davis,
CA, USA.
REFERENCE: Insect Mol Biol 2005 Apr 14(2):145-50
Abstract SP-15 is a sandfly salivary protein that provides strong
protection against cutaneous leishmaniasis, caused by Leishmania major,
and has been proposed as a potential vaccine against this disease. To
investigate possible antigenic variation in this protein, we examined
genetic polymorphism of SP-15 in 100 Phlebotomus papatasi sandflies,
from a natural population from Sudan and four laboratory colonies from
Egypt, Jordan, Israel and Saudi Arabia. We found that although many
variants of SP-15 may be found in nature, differences among them are
minimal (mean +/- SD pairwise differences = 1.69 +/- 0.83% for forty
nucleotide sequences and 3.06 +/- 1.13% for thirty amino acid sequence
variants). Analysis of proportions of synonymous and non-synonymous
substitutions indicated that SP-15 is not under diversifying selection.
Our results suggest that a vaccine based on SP-15 protein should result
in a uniform immune response.
PMID: 15797810
TITLE: Immunopathogenesis of infection with the visceralizing Leishmania
species.
AUTHORS: Mary E Wilson, Selma M B Jeronimo, Richard D Pearson
AFFILIATION: Departments of Internal Medicine, Microbiology and Epidemiology,
University of Iowa, The VA Medical Center, Iowa City, IA, USA.
REFERENCE: Microb Pathog 2005 Apr 38(4):147-60
Human leishmaniasis is a spectral disease that includes asymptomatic
self-resolving infection, localized skin lesions, and progressive
visceral leishmaniasis. With some overlap, visceral and cutaneous
leishmaniasis are usually caused by different species of Leishmania.
This review focuses on host responses to infection with the species that
cause visceral leishmaniasis, as they contrast with species causing
localized cutaneous leishmaniasis. Data from experimental models
document significant differences between host responses to organisms
causing these diverse syndromes. The visceralizing Leishmania spp. cause
localized organ-specific immune responses that are important
determinants of disease outcome. Both the Leishmania species causing
cutaneous and those causing visceral leishmaniasis require a Type 1
immune response to undergo cure in mouse models. However, during
progressive murine infection with the visceralizing Leishmania sp., the
Type 1 response is suppressed at least in part by TGF-beta and IL-10
without type 2 cytokine production. This contrasts with the cutaneous
species L. major, in which a Type 2 response suppresses type 1 cytokines
and leads to murine disease progression. Population and family studies
are beginning to elucidate human genetic determinants predisposing to
different outcomes of Leishmania infection. These studies should
eventually result in a better understanding of the immunopathogenesis
and the spectrum of human leishmaniasis.
PMID: 15806230
TITLE: Contribution study of visceral leishmaniasis in Syria.
AUTHORS: Samar Al-Nahhas, Maha Shaaban, Lana Hammoud
AFFILIATION: Professor, Faculty of Sciences, Damascus University, PO Box 10718,
Damascus, Syria. Tel. +963 (11) 3716872. Fax. +963 (11) 3732338. E-mail:
samar at scs-net.org.
REFERENCE: Saudi Med J 2005 Mar 26(3):490-2
PMID: 15682458
TITLE: The fate of heterologous CD4+ T cells during Leishmania donovani
infection.
AUTHORS: Rosalind Polley, Soombul Zubairi, Paul M Kaye
AFFILIATION: Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, London, UK.
REFERENCE: Eur J Immunol 2005 Feb 35(2):498-504
Little is currently understood about the consequences of chronic
parasitic infection for the fate of memory CD4+ T cells that recognize
heterologous antigens, e.g. resulting from prior infections or
vaccination. Here, we address how Leishmania donovani infection affected
the fate of non-cross-reactive (OVA)-specific memory CD4+ T cells. DO11
cells were adoptively transferred into naive recipient mice, which were
then immunized to generate memory DO11 cells. After 6 weeks, mice were
infected with L. donovani and the fate of DO11 cells was determined. L.
donovani infection stimulated an approximately threefold expansion in
the total number of CD4+ T cells and DO11 cells, compared to that
observed in uninfected mice. DO11 T cells were more actively dividing in
infected mice, as judged by 5-bromo-2' deoxyuridine labeling, whereas
their rate of apoptosis in control and infected mice was identical. Both
CD45RBhiCD44lo naive T cells and to a greater extent CD45RBloCD44hi
memory DO11 cells increased in number in the spleens of infected mice,
whereas no changes occurred to DO11 cell number or phenotype in the
draining lymph nodes. These data indicate that heterologous CD4+ T cells
may actively divide during chronic infectious diseases, with important
implications for how chronic infection may impact on heterologous
immunity.
PMID: 15657947
TITLE: A critical role for lipophosphoglycan in proinflammatory responses of
dendritic cells to Leishmania mexicana.
AUTHORS: Toni Aebischer, Clare L Bennett, Mattia Pelizzola, Caterina
Vizzardelli, Norman Pavelka, Matteo Urbano, Monica Capozzoli, Alessandra
Luchini, Thomas Ilg, Francesca Granucci, C Clare Blackburn, Paola
Ricciardi-Castagnoli
AFFILIATION: Max-Planck-Institute for Infection Biology, Department of Molecular
Biology, Berlin, Germany.
REFERENCE: Eur J Immunol 2005 Feb 35(2):476-86
Recognition of pathogen-associated molecular patterns (PAMP) influences
the response of dendritic cells (DC) and therefore development of innate
and adaptive immunity. Different forms of Leishmania mexicana have
distinct effects on DC, with promastigotes and amastigotes being
activating and apparently neutral, respectively. We investigated whether
stage-specific differences in surface composition might account for
these distinct effects. Amastigotes and promastigotes lacking the lpg1
gene needed for lipophosphoglycan (LPG) biosynthesis could not activate
DC in vitro. Genome-wide transcriptional profiling of DC infected with
wild-type or mutant promastigotes or wild-type amastigotes revealed that
wild-type promastigotes induce an inflammatory signature that is
lacking in DC exposed to the other parasite forms. The proinflammatory
response pattern was partly recovered by reconstitution of lpg1
expression in lpg1-/- parasites, and exposure to purified LPG increased
the expression of MHC class II and CD86 on DC. Infection with wild-type
but not lpg1-/- promastigotes increased the number of activated DC in
draining lymph nodes, and this was correlated with lower early parasite
burdens in wild-type-infected animals. These in vivo and in vitro
results suggest an LPG-dependent activation of DC that contributes to
host defense and agree with the notion that the parasites evolved under
immune pressure to down-regulate PAMP expression in mammalian hosts.
PMID: 15785061
TITLE: Cutaneous leishmaniasis caused by Leishmania tropica: treatment with oral
fluconazole.
AUTHORS: E Laffitte, B Genton, R G Panizzon
REFERENCE: Dermatology 2005 210(3):249-51
PMID: 15715010
TITLE: Detection of Leishmania infantum in canine peripheral blood.
AUTHORS: V Foglia Manzillo, D Piantedosi, L Cortese
AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Sezione Clinica
Medica, Università degli Studi di Napoli Federico II, via F. Delpino 1,80137
Naples, Italy.
REFERENCE: Vet Rec 2005 Jan 156(5):151-2
PMID: 15736529
TITLE: [Visceral leishmaniases]
AUTHORS: Eric Rosenthal, Pierre Marty
AFFILIATION: Service de médecine interne, hôpital de l'Archet, CHU de Nice,
06202 Nice Cedex. rosenthal.e at chu-nice.fr
REFERENCE: Rev Prat 2004 Dec 54(20):2211-6
Visceral leishmaniases (VL), with spreading epidemics in India and Sudan
, and sporadic cases in mediterranean basin, show clinical,
therapeutical and public health aspects varying according to the
geographic context. Co-infection of VL with the human immunodeficiency
virus emerged in southwestern Europe and could occur in a next future in
India, in Sudan, in Ethiopia or in Brazil. Today, lipid formulations of
amphotericin B should be the first line drugs in Mediterranean basin.
Elsewhere, pentavalent antimonials remain the cornerstone of treatment
in non resistant areas, conventional amphotericin B or miltefosine being
an alternative in areas of resistance to antimony.
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PMID: 12574369
TITLE: NF-kappa B1 is required for optimal CD4+ Th1 cell development and
resistance to Leishmania major.
AUTHORS: David Artis, Kendra Speirs, Karen Joyce, Michael Goldschmidt, Jorge
Caamaño, Christopher A Hunter, Phillip Scott
AFFILIATION: Department of Pathobiology, School of Veterinary Medicine,
University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
REFERENCE: J Immunol 2003 Feb 170(4):1995-2003
The NF-kappaB family of transcription factors regulates the expression
of a wide range of immune response genes involved in immunity to
pathogens. However, the need for individual family members in regulating
innate and adaptive immune responses in vivo has yet to be clearly
defined. We investigated the role of NF-kappaB1 in the induction of
protective IL-12-dependent Th1 cell responses following infection with
the intracellular protozoan parasite Leishmania major. Whereas wild-type
C57BL/6 mice controlled parasite replication, NF-kappaB1 knockout (KO)
mice were susceptible to infection, developing chronic unresolving
lesions associated with persistent parasites. There was a profound
defect in Ag-specific CD4(+) T cell proliferation and IFN-gamma
production in infected KO mice, although innate responses-including IL-
12 production and control of intracellular parasite replication by
macrophages-were intact. In vitro polyclonal stimulation of purified
naive KO T cells revealed an intrinsic defect in CD4(+) T cell
proliferation associated with reduced IL-2 receptor expression, but
operating independently of APC function and IL-2 production. Critically
, the frequency of proliferating KO CD4(+) T cells secreting IFN-gamma
matched that of wild-type cells, suggesting that NF-kappaB1 was not
required for efficient transcription of the IFN-gamma gene. Taken
together, these results identify a novel role for NF-kappaB1 in CD4(+) T
cell proliferation and the development of Th1 cell responses required
for protective immunity against intracellular pathogens.
PMID: 11970983
TITLE: NF-kappa B2 is required for optimal CD40-induced IL-12 production but
dispensable for Th1 cell Differentiation.
AUTHORS: Kendra Speirs, Jorge Caamano, Michael H Goldschmidt, Christopher A
Hunter, Phillip Scott
AFFILIATION: Department of Pathobiology, University of Pennsylvania,
Philadelphia, PA 19104, USA.
REFERENCE: J Immunol 2002 May 168(9):4406-13
NF-kappa B is a ubiquitously expressed transcription factor involved in
the regulation of innate and adaptive immunity. As part of studies to
define the role of various NF-kappa B family members in Th cell
development and maintenance, we infected NF-kappa B2(-/-) and control
mice with Leishmania major and followed disease progression. NF-kappa B2
(-/-) mice on a normally resistant background develop chronic nonhealing
lesions associated with uncontrolled parasite replication and a failure
to develop an IFN-gamma response. We show that there are no intrinsic
defects in Th cell differentiation in the absence of NF-kappa B2. Indeed
, NF-kappa B2(-/-) T cells are able to develop a Th1 phenotype and
protect recombination-activating gene(-/-) mice from progressive
cutaneous leishmaniasis. We demonstrate instead that the susceptibility
of NF-kappa B2(-/-) mice to L. major is the result of an IL-12
deficiency, and we provide evidence for a specific impairment in CD40-
induced IL-12 production by macrophages lacking this transcription
factor.
PMID: 15424995
TITLE: Visceral leishmaniasis.
AUTHORS: W C CACCAMISE
REFERENCE: U S Armed Forces Med J 1950 Jun 1(6):661-4
REQUEST: [ leishmania ]
(18 articles match this request. 5 articles matching other requests removed)
PMID: 15804377
TITLE: Flow cytometric assessment of Leishmania spp metacyclic differentiation:
Validation by morphological features and specific markers.
AUTHORS: Elvira M Saraiva, Lucia H Pinto-da-Silva, João Luiz M Wanderley,
Adriana C Bonomo, Marcello A Barcinski, Maria Elisabete C Moreira
AFFILIATION: Instituto de Microbiologia, Universidade Federal do Rio de Janeiro,
Rio de Janeiro, Brazil.
REFERENCE: Exp Parasitol 2005 May 110(1):39-47
Characterization of infective metacyclic promastigotes of Leishmania spp
can be an essential step in several experimental protocols. Metacyclic
forms of all Leishmania species display a typical morphology with short
, narrow cell body, and an elongated flagellum. This feature suggests
that metacyclics can be distinguished from procyclic forms by non-
fluorimetric flow cytometric parameters thus enabling the follow-up of
their appearance and acquisition of specific properties, during
metacyclogenesis in in vitro cultures. Here we describe the flow
cytometric parameters of stage-specific promastigotes of Leishmania
major, Leishmania donovani, Leishmania amazonensis, and Leishmania
braziliensis. Our findings were validated by optical microscopy
morphology and specific procyclic labeling with FITC-peanut agglutinin.
Furthermore, we show that parasite's distribution in the plot during
differentiation in culture is not species specific and that the
parasites displaying low forward-angle light scatter (FSC(low)) are
three times more infective than the FSC(high) ones. The method here
described can be applied to the identification of metacyclics of
different Leishmania spp within the whole stationary population.
PMID: 15797809
TITLE: Exploiting calnexin expression on phagosomes to isolate Leishmania
parasitophorous vacuoles.
AUTHORS: Peter E Kima, Waltraud Dunn
AFFILIATION: Department of Microbiology and Cell Science, University of Florida,
Building 981, Box 110700, Gainesville, FL 32611, USA.
REFERENCE: Microb Pathog 2005 Apr 38(4):139-45
We have developed a simple scheme for the isolation of parasitophorous
vacuoles (PVs) that harbor Leishmania parasites. This scheme exploits
the observation that PVs display endoplasmic reticulum molecules,
including the transmembrane protein calnexin. The presence of calnexin
at the surface of the PVs distinguishes them from late endosomal
vesicles of comparable density. As a result, PVs can be isolated by
calnexin affinity selection from an enriched PV fraction obtained by
sucrose density fractionation.
PMID: 15784607
TITLE: Leishmania major modulates chemokine and chemokine receptor expression by
dendritic cells and affects their migratory capacity.
AUTHORS: Mario Steigerwald, Heidrun Moll
AFFILIATION: Institut für Molekulare Infektionsbiologie, Universität
Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
REFERENCE: Infect Immun 2005 Apr 73(4):2564-7
Dendritic cells (DC) both produce and respond to chemokines. We examined
the profiles of chemokines and chemokine receptors expressed by DC and
their chemotactic response after interaction with Leishmania major.
Expression of the chemokine receptors CCR2 and CCR5 by DC and their
responsiveness to the respective ligands, CCL2 and CCL3, were
downregulated, while the level of CCR7 and the DC response to its ligand
CCL21 were enhanced. These parasite-induced alterations were observed
with DC from L. major-resistant and -susceptible mice. In contrast,
expression of the chemokine CXCL10 was elicited only in DC from L. major
-resistant mice.
PMID: 15784551
TITLE: Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania
mexicana lesions.
AUTHORS: Laurence U Buxbaum, Phillip Scott
AFFILIATION: Department of Pathobiology, University of Pennsylvania School of
Veterinary Medicine, 216 ROS, 3800 Spruce Street, Philadelphia, PA 19104, USA.
REFERENCE: Infect Immun 2005 Apr 73(4):2101-8
Infection of C57BL/6 (B6) mice with Leishmania mexicana is associated
with a minimal immune response and chronic disease. Here we show that B6
interleukin 10-/- (IL-10-/-) mice resolve their lesions and exhibit
increased gamma interferon (IFN-gamma), nitric oxide production, and
delayed-type hypersensitivity. This enhanced resistance was dependent
upon IL-12p40, since treatment of L. mexicana-infected IL-10-/- mice
with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-
opsonized L. mexicana induced IL-10 production by B6 macrophages in
vitro, implicating antibody binding to Fc receptors as a mechanism
involved in IL-10 production in this infection. Furthermore, B6 FcRgamma
-/- mice resolve L. mexicana lesions, and lymph node cells from these
mice produced less IL-10 and more IFN-gamma than cells from infected
wild-type mice. These data demonstrate that removal of IL-10 or FcgammaR
leads to resolution of L. mexicana disease and support a model in which
ligation of FcgammaR by L. mexicana-bound immunoglobulin G promotes IL-
10 production, leading to chronic disease.
PMID: 15788098
TITLE: Heterologous expression of the filarial nematode alt gene products
reveals their potential to inhibit immune function.
AUTHORS: Natalia Gomez-Escobar, Clare Bennett, Lidia Prieto-Lafuente, Toni
Aebischer, Clare C Blackburn, Rick M Maizels
AFFILIATION: Institute of Immunology and Infection Research, University of
Edinburgh, UK. r.maizels at ed.ac.uk.
REFERENCE: BMC Biol 2005 Mar 3(1):8
BACKGROUND: Parasites exploit sophisticated strategies to evade host
immunity that require both adaptation of existing genes and evolution of
new gene families. We have addressed this question by testing the
immunological function of novel genes from helminth parasites, in which
conventional transgenesis is not yet possible. We investigated two such
novel genes from Brugia malayi termed abundant larval transcript (alt),
expression of which reaches ~5% of total transcript at the time
parasites enter the human host. RESULTS: To test the hypothesis that ALT
proteins modulate host immunity, we adopted an alternative transfection
strategy to express these products in the protozoan parasite Leishmania
mexicana. We then followed the course of infection in vitro in
macrophages and in vivo in mice. Expression of ALT proteins, but not a
truncated mutant, conferred greater infectivity of macrophages in vitro
, reaching 3-fold higher parasite densities. alt-transfected parasites
also caused accelerated disease in vivo, and fewer mice were able to
clear infection of organisms expressing ALT. alt-transfected parasites
were more resistant to IFN-gamma-induced killing by macrophages.
Expression profiling of macrophages infected with transgenic L. mexicana
revealed consistently higher levels of GATA-3 and SOCS-1 transcripts,
both associated with the Th2-type response observed in in vivo filarial
infection. CONCLUSION: Leishmania transfection is a tractable and
informative approach to determining immunological functions of single
genes from heterologous organisms. In the case of the filarial ALT
proteins, our data suggest that they may participate in the Th2 bias
observed in the response to parasite infection by modulating cytokine-
induced signalling within immune system cells.
PMID: 15725130
TITLE: A simple method allowing DIC imaging in conjunction with confocal
microscopy.
AUTHORS: S H Cody, S D Xiang, M J Layton, E Handman, M H C Lam, J E Layton, E C
Nice, J K Heath
AFFILIATION: Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne
Hospital, Victoria 3050, Australia. stephen.cody at ludwig.edu.au
REFERENCE: J Microsc 2005 Mar 217(Pt 3):265-74
Current optical methods to collect Nomarski differential interference
contrast (DIC) or phase images with a transmitted light detector (TLD)
in conjunction with confocal laser scanning microscopy (CLSM) can be
technically challenging and inefficient. We describe for the first time
a simple method that combines the use of the commercial product QPm (
Iatia, Melbourne Australia) with brightfield images collected with the
TLD of a CLSM, generating DIC, phase, Zernike phase, dark-field or
Hoffman modulation contrast images. The brightfield images may be
collected at the same time as the confocal images. This method also
allows the calculation of contrast-enhanced images from archival data.
The technique described here allows for the creation of contrast-
enhanced images such as DIC or phase, without compromising the intensity
or quality of confocal images collected simultaneously. Provided the
confocal microscope is equipped with a motorized z-drive and a TLD, no
hardware or optical modifications are required. The contrast-enhanced
images are calculated with software using the quantitative phase-
amplitude microscopy technique (Barone-Nugent et al., 2002). This
technique, being far simpler during image collection, allows the
microscopist to concentrate on their confocal imaging and experimental
procedures. Unlike conventional DIC, this technique may be used to
calculate DIC images when cells are imaged through plastic, and without
the use of expensive strain-free objective lenses.
PMID: 15796010
TITLE: Identification of the first pyrimidine nucleobase transporter in
Leishmania: similarities with the Trypanosoma brucei U1 transporter and
antileishmanial activity of uracil analogues.
AUTHORS: I G Papageorgiou, L Yakob, M I Al Salabi, G Diallinas, K P Soteriadou,
H P De Koning
AFFILIATION: Department of Biochemistry, Hellenic Pasteur Institute, 115 21
Athens, Greece.
REFERENCE: Parasitology 2005 Mar 130(Pt 3):275-83
While purine transport has been widely studied in protozoa, almost
nothing is known about their capacity to salvage pyrimidines. Here, we
report a Leishmania major transporter with high affinity for uracil (Km=
0.32+/-0.07 microM) which we designated LmU1. This transporter displayed
a high degree of specificity, as it had virtually no affinity for
cytosine, thymine or purine nucleobases, nor did it transport pyrimidine
nucleosides. Highest affinity was for 5-fluorouracil. The results show
that the permeant binding site of LmU1 interacts strongly with the keto
groups of uracil, as shown by a low affinity for 2-thio- and 4-
thiouracil. LmU1 appears to further bind uracil through a weak hydrogen
bond with N(1)H of the pyrimidine ring in addition to a stronger H-bond
with N(3)H. Substrate binding and selectivity were strikingly similar to
that of the U1 transporter in the related kinetoplastid Trypanosoma
brucei. Uracil analogues likely to be transported by LmU1 were also
screened for antileishmanial activity, with 5-fluorouracil displaying
strong activity against promastigotes and intracellular amastigotes.
Overall, the results show that, like purine nucleobase transport,
pyrimidine nucleobase transport function is very similar in L. major and
T. brucei insect forms.
PMID: 15781861
TITLE: Functional complementation of Trypanosoma brucei RNA in vitro editing
with recombinant RNA ligase.
AUTHORS: Guanghan Gao, Agda M Simpson, Xuedong Kang, Kestrel Rogers, Martina
Nebohacova, Feng Li, Larry Simpson
AFFILIATION: Department of Microbiology, Immunology, and Molecular Genetics and
Howard Hughes Medical Institute, University of California, Los Angeles, CA
90095.
REFERENCE: Proc Natl Acad Sci U S A 2005 Mar 102(13):4712-7
The approximately 20S RNA ligase-containing complex (L-complex) in
trypanosomatid mitochondria interacts by means of RNA linkers with at
least two other multiprotein complexes to mediate the editing of
mitochondrial cryptogene transcripts. The L-complex contains
approximately 16 proteins, including the two RNA-editing ligases (RELs
), REL1 and REL2. Leishmania tarentolae REL1 and REL2 and Trypanosoma
brucei REL1 were expressed as enzymatically active tandem affinity
purification-tagged proteins in a Baculovirus system. When these
proteins were added to mitochondrial lysates from T. brucei procyclic
cells that were depleted of the cognate endogenous ligase by RNA
interference down-regulation of expression, the added proteins were
integrated into the L-complex, and, in the case of REL1, there was a
complementation of in vitro-precleaved U-insertion and U-deletion
editing activities of the 20S L-complex. Integration of the recombinant
proteins did not occur or occurred at a very low level with noncognate
ligase-depleted L-complex or with wild-type L-complex. A C-terminal
region of the T. brucei recombinant REL1 downstream of the catalytic
domain was identified as being involved in integration into the L-
complex. The ability to perform functional complementation in vitro
provides a powerful tool for molecular dissection of the editing
reaction.
PMID: 15799523
TITLE: Isolation of a myoinhibitory peptide from Leishmania major
(Kinetoplastida: Trypanosomatidae) and its function in the vector sand fly
Phlebotomus papatasi (Diptera: Psychodidae).
AUTHORS: Rajeev Vaidyanathan
AFFILIATION: Department of Parasitology, Hebrew University of Jerusalem,
Hadassah Medical School, Ein Kerem, Jerusalem 91120, Israel.
REFERENCE: J Med Entomol 2005 Mar 42(2):142-52
Protozoan parasites in the genus Leishmania are ingested by sand flies
with blood and multiply in the gut until they are transmitted to a
vertebrate host when the sand fly blood feeds again. Infections of the
enzootic vector Phlebotomus papatasi Scopoli result in distended midguts
with no spontaneous gut contractions. Using a P. papatasi hindgut
contraction bioassay, a paralytic factor sensitive to trypsin,
chymotrypsin, proteinase-K, and heating at 56 degrees C was detected in
crude lysates of Leishmania major promastigotes. Application of parasite
lysate to isolated hindguts resulted in reversible, dose-dependent
inhibition of spontaneous contractions. Mean volume of isolated midguts
and hindguts increased by 50-60% after application of L. major lysate. L
. major paralytic factor was purified 10(4)-fold over the total protein
preparation and yielded a hydrophobic 12-kDa peptide. Myoinhibitory
activity eluted as a single peak in reverse phase-high-pressure liquid
chromatography. Tandem mass spectrometry resulted in 15 amino acid
sequences, three of them sharing 45-73% homology with short hypothetical
gene products of undefined function from Pseudomonas, Halobacterium,
and Drosophila. This unique protozoan peptide mimics the function of
endogenous insect neuropeptides that control visceral muscle
contractions. By this novel mechanism, parasites persist in the expanded
, relaxed midgut after blood meal and peritrophic matrix digestion. This
allows time for development and migration of infective forms,
facilitating sand fly vector competence and parasite transmission.
PMID: 15557260
TITLE: Structural and functional analysis of the gpsA gene product of
Archaeoglobus fulgidus: a glycerol-3-phosphate dehydrogenase with an unusual
NADP+ preference.
AUTHORS: Shin-Ichi Sakasegawa, Christoph H Hagemeier, Rudolf K Thauer, Lars-O
Essen, Seigo Shima
AFFILIATION: Max-Planck-Institut für terrestrische Mikrobiologie and
Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps Universität,
Marburg, Germany.
REFERENCE: Protein Sci 2004 Dec 13(12):3161-71
NAD(+)-dependent glycerol-3-phosphate dehydrogenase (G3PDH) is generally
absent in archaea, because archaea, unlike eukaryotes and eubacteria,
utilize glycerol-1-phosphate instead of glycerol-3-phosphate for the
biosynthesis of membrane lipids. Surprisingly, the genome of the
hyperthermophilic archaeon Archaeoglobus fulgidus comprises a G3PDH
ortholog, gpsA, most likely due to horizontal gene transfer from a
eubacterial organism. Biochemical characterization proved G3PDH-like
activity of the recombinant gpsA gene product. However, unlike other
G3PDHs, the up to 85 degrees C thermostable A. fulgidus G3PDH exerted a
15-fold preference for NADPH over NADH. The A. fulgidus G3PDH bears the
hallmarks of adaptation to halotolerance and thermophilicity, because
its 1.7-A crystal structure showed a high surface density for negative
charges and 10 additional intramolecular salt bridges compared to a
mesophilic G3PDH structure. Whereas all amino acid residues required for
dihydroxyacetone phosphate binding and reductive catalysis are highly
conserved, the binding site for the adenine moiety of the NAD(P)
cosubstrate shows a structural variation that reflects the observed
NADPH preference, for example, by a putative salt bridge between R49 and
the 2'-phosphate.
PMID: 15615399
TITLE: [Alithiasic cholecystitis in association with visceral leishmaniasis in
an immunodepressed patient]
AUTHORS: T Coton, P Kraemer, F Simon, J J Morand, J J Depina, T Lonjon, P
Hovette
REFERENCE: Med Trop (Mars) 2004 64(4):407-8
********************************************************************************************************************
The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
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PMID: 15550118
TITLE: Novel adjuvant based on a proteoliposome-derived cochleate structure
containing native lipopolysaccharide as a pathogen-associated molecular
pattern.
AUTHORS: Oliver Pérez, Gustavo Bracho, Miriam Lastre, Nestor Mora, Judith del
Campo, Danay Gil, Caridad Zayas, Reinaldo Acevedo, Domingo González, José A
López, Carlos Taboada, Cameron Turtle, Rosa L Solis
AFFILIATION: Immunology Department, Finlay Institute, Havana, Cuba.
oliverp at finlay.edu.cu
REFERENCE: Immunol Cell Biol 2004 Dec 82(6):603-10
Proteoliposomes (PL) from Neisseria meningitidis B have been widely used
as a core antigen for antimeningococcal vaccination. PL contain major
outer membrane proteins, LPS and phospholipids, and they induce a strong
Th1 immune response, but they have low stability in solution. Attending
to the need for new vaccine adjuvants, we developed a highly stable
cochleate structure (CS) from PL using a technology that allows easy
incorporation of new antigens. We explored the ability of PLCS to
activate the immune system and its possible application as an adjuvant
for parenteral and mucosal routes. Our results showed that PLCS were
able to upregulate the expression of MHC class II and costimulatory
molecules on human dendritic cells, as well as being able to stimulate
the production of soluble mediators of a Th1 response, such as IL-12 and
nitric oxide. High levels of anti-PL IgG were detected in serum after i
.m. or mucosal (oral and nasal) administration, but also anti-PL
secretory IgA was produced in saliva following nasal delivery. The
immune response polarization to a Th1 pattern was confirmed by the
induction of IgG2a antibodies, positive delayed type hypersensitivity
reactions, and IFN-gamma production by splenocytes from immunized mice.
The adjuvant potential was explored using PLCS containing ovalbumin (Ova
). PLCS-Ova was able to elicit a substantial increase in anti-Ova IgG
compared with Ova alone. In addition, a significant reduction in lesion
size was observed in mice immunized with Leishmania major antigens in
PLCS after challenge with virulent protozoa, suggesting at least partial
modulation of the Th2 environment induced by this parasite. In
conclusion, our results support the use of PLCS as a potent Th1 adjuvant
for parenteral and mucosal vaccines.
PMID: 15102766
TITLE: Leishmania major amastigotes induce p50/c-Rel NF-kappa B transcription
factor in human macrophages: involvement in cytokine synthesis.
AUTHORS: Lamia Guizani-Tabbane, Khadija Ben-Aissa, Meriam Belghith, Atfa Sassi,
Koussay Dellagi
AFFILIATION: Laboratory of Immunology, Vaccinology and Molecular Genetics (WHO
Collaborating Center for Research and Training in Leishmaniasis), Institut
Pasteur de Tunis, 1002 Tunis-Belvedere, Tunisia. lamia.guizani at Pasteur.rns.tn
REFERENCE: Infect Immun 2004 May 72(5):2582-9
Invasion of a host by pathogens is frequently associated with activation
of nuclear factor kappa B (NF-kappaB), which is implicated in various
aspects of immune function required for resistance to infection. However
, pathogens may also subdue these mechanisms to secure their survival.
Here we describe the effect of Leishmania major infection on NF-kappaB
transcription factor activation in both promonocytic human cell line
U937 and fresh human monocytes. Infection by L. major amastigotes
blocked nuclear translocation of a phorbol-12 myristate-13 acetate (PMA
)-induced p50/p65 NF-kappaB complex in PMA-treated differentiated U937
cells and triggered expression of p50- and c-Rel-containing complexes in
both U937 cells and fresh human monocytes. These p50/c-Rel complexes,
triggered by direct cell-parasite interactions, were detectable within
30 min after the interaction and were transcriptionally active. The NF-
kappaB inhibitor caffeic acid phenethyl ester inhibited production of
both tumor necrosis factor alpha and interleukin-10 (IL-10) induced by
Leishmania amastigotes in differentiated U937 cells. Similar results for
IL-10 induction were observed with amastigote-infected human monocytes
. Our results indicate that L. major amastigotes activate NF-kappaB by
specifically inducing p50- and c-Rel-containing complexes which are
likely involved in the regulation of cytokine synthesis.
REQUEST: [ sand fly ]
(2 articles match this request. 2 articles matching other requests removed)
REQUEST: [ sandfly ]
(2 articles match this request. 1 article matching other requests removed)
PMID: 15708593
TITLE: Development of a mouse model for the study of Toscana virus
pathogenesis.
AUTHORS: Maria Grazia Cusi, Gianni Gori Savellini, Chiara Terrosi, Giuseppa Di
Genova, Marcello Valassina, Melissa Valentini, Sabrina Bartolommei, Clelia
Miracco
AFFILIATION: Department of Molecular Biology, Virology Section, University of
Siena, Policlinico Le Scotte, V.le Bracci, Building V, 53100 Siena, Italy.
cusi at unisi.it
REFERENCE: Virology 2005 Mar 333(1):66-73
Toscana virus (TOSV) has recently been recognized as an emerging virus
transmitted by phlebotomus vectors, responsible for acute neurological
diseases in Mediterranean countries. In our study, we demonstrated that
adult Balb/c mice were susceptible to TOSV when infected intracerebrally
(i.c.) or subcutaneously (s.c.) with a neuroadapted strain of the virus
. We have shown that by performing serial passages of a wild type human
isolate of TOSV in mouse brains, selection occurs for a highly virulent
variant which replicates efficiently in the central nervous system (CNS
) of i.c.-injected mice, causing acute encephalitis and death.
Immunohistochemical analysis and TUNEL assay of post-mortem organs
showed that TOSV replication was highly restricted to neurons in which
it induced apoptotic death; however, virus antigen-positivity was also
observed in the spleen and lymph nodes. In s.c.-injected mice, virus was
detectable in the spleen and lymph nodes, whereas only few meningeal
cells and neurons were affected, allowing for the mouse survival the
infection. The presence of TOSV in spleen and lymph node cells in both s
.c.- and i.c.-treated mice suggests their possible involvement in the
diffusion of the infection. This animal model may be helpful for the
development of prophylactic measures against TOSV infections.
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