title: Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major.
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.
authors.affiliation: Faculty of Medicine, Department of Immunology, Imperial College London, London, United Kingdom.
authors.forename: Pascale
authors.initials: P
authors.lastname: Kropf
authors.forename: Marina A
authors.initials: MA
authors.lastname: Freudenberg
authors.forename: Manuel
authors.initials: M
authors.lastname: Modolell
authors.forename: Helen P
authors.initials: HP
authors.lastname: Price
authors.forename: Shanti
authors.initials: S
authors.lastname: Herath
authors.forename: Simone
authors.initials: S
authors.lastname: Antoniazi
authors.forename: Chris
authors.initials: C
authors.lastname: Galanos
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Smith
authors.forename: Ingrid
authors.initials: I
authors.lastname: Müller
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D018320:Leishmania major / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001119:Arginase