title: The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent.
abstract: The initial host response toward the extracellular parasite Trypanosoma brucei is characterized by the early release of inflammatory mediators associated with a type 1 immune response. In this study, we show that this inflammatory response is dependent on activation of the innate immune system mediated by the adaptor molecule MyD88. In the present study, MyD88-deficient macrophages are nonresponsive toward both soluble variant-specific surface glycoprotein (VSG), as well as membrane-bound VSG purified from T. brucei. Infection of MyD88-deficient mice with either clonal or nonclonal stocks of T. brucei resulted in elevated levels of parasitemia. This was accompanied by reduced plasma IFN-gamma and TNF levels during the initial stage of infection, followed by moderately lower VSG-specific IgG2a Ab titers during the chronic stages of infection. Analysis of several TLR-deficient mice revealed a partial requirement for TLR9 in the production of IFN-gamma and VSG-specific IgG2a Ab levels during T. brucei infections. These results implicate the mammalian TLR family and MyD88 signaling in the innate immune recognition of T. brucei.
authors.affiliation: Immunology of Infectious Disease Medical Research Council/University of Cape Town Unit, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa. mdrennan@uctgsh1.uct.ac.za
authors.forename: Michael B
authors.initials: MB
authors.lastname: Drennan
authors.forename: Benoît
authors.initials: B
authors.lastname: Stijlemans
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Abbeele
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Quesniaux
authors.forename: Mark
authors.initials: M
authors.lastname: Barkhuizen
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Stefan
authors.initials: S
authors.lastname: Magez
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000276:immunology / Q000469:parasitology; D002478:Cells, Cultured; D016054:DNA, Protozoan / Q000502:physiology; D007113:Immunity, Innate / Q000235:genetics; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D018512:Parasitemia / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D012995:Solubility; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016054:DNA, Protozoan; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014643:Variant Surface Glycoproteins, Trypanosoma