The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent.

TitleThe induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent.
Publication TypeJournal Article
Year of Publication2005
AuthorsDrennan, M. B., B. Stijlemans, J. Van Den Abbeele, V. J. Quesniaux, M. Barkhuizen, F. Brombacher, P. De Baetselier, B. Ryffel, and S. Magez
JournalJ Immunol
Date Published2005 Aug 15
KeywordsAdaptor Proteins, Signal Transducing, Animals, Antigens, Differentiation, Cell Membrane, Cells, Cultured, DNA, Protozoan, Immunity, Innate, Macrophage Activation, Macrophages, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Myeloid Differentiation Factor 88, Parasitemia, Receptors, Immunologic, Signal Transduction, Solubility, Toll-Like Receptor 9, Trypanosoma brucei brucei, Trypanosomiasis, African, Variant Surface Glycoproteins, Trypanosoma

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.

Alternate JournalJ. Immunol.
PubMed ID16081822
Grant List / / Wellcome Trust / United Kingdom