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PMID: 15039311 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major.

Infection and immunity ·Vol. 72 ·No. 4 ·2004-04-00 ·Pages 1920-8

Kropf P, Freudenberg MA, Modolell M, Price HP, Herath S, Antoniazi S, Galanos C, Smith DF, Müller I

Abstract

The essential role of Toll-like receptors (TLR) in innate immune responses to bacterial pathogens is increasingly recognized, but very little is known about the role of TLRs in host defense against infections with eukaryotic pathogens. For the present study, we investigated whether TLRs contribute to the innate and acquired immune response to infection with the intracellular protozoan parasite Leishmania major. Our results show that TLR4 contributes to the control of parasite growth in both phases of the immune response. We also addressed the mechanism that results in killing or growth of the intracellular parasites. Control of parasite replication correlates with the early induction of inducible nitric oxide synthase in TLR4-competent mice, whereas increased parasite survival in host cells from TLR4-deficient mice correlates with a higher activity of arginase, an enzyme known to promote parasite growth. This is the first study showing that TLR4 contributes to the effective control of Leishmania infection in vivo.

MeSH Terms
Animals Arginase/metabolism Cells, Cultured Cytokines/metabolism Female Humans Leishmania major/pathogenicity Leishmaniasis, Cutaneous/immunology,parasitology Macrophages/parasitology Male Membrane Glycoproteins/genetics,metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Nitric Oxide Synthase/metabolism Nitric Oxide Synthase Type II Receptors, Cell Surface/genetics,metabolism Toll-Like Receptor 4 Toll-Like Receptors
Chemicals
Cytokines Membrane Glycoproteins Receptors, Cell Surface TLR4 protein, human Toll-Like Receptor 4 Toll-Like Receptors NOS2 protein, human Nitric Oxide Synthase Nitric Oxide Synthase Type II Nos2 protein, mouse Arginase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kropf Pascale
Faculty of Medicine, Department of Immunology, Imperial College London, London, United Kingdom.
Freudenberg Marina A
Modolell Manuel
Price Helen P
Herath Shanti
Antoniazi Simone
Galanos Chris
Smith Deborah F
Müller Ingrid
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.72.4.1920-1928.2004
Published
2004-04-00
Pages
1920-8
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC375159
Subset
IM
Grants
Wellcome Trust · 061343 · United Kingdom
External Links
PubMed source DOI: 10.1128/IAI.72.4.1920-1928.2004 PMC Full Text View journal details
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