Cutting Edge: TLR9 and TLR2 Signaling Together Account for MyD88-Dependent Control of Parasitemia in Trypanosoma cruzi Infection

Journal of Immunology - Tập 177 Số 6 - Trang 3515-3519 - 2006
André Báfica1, Helton Costa Santiago2, Romina S. Goldszmid1, Catherine Ropert3, Ricardo T. Gazzinelli2,3, Alan Sher1
1*Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
2Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
3‡Laboratório de Imunopatologia, CPqRR, FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil

Tóm tắt

Abstract Activation of innate immune cells by Trypanosoma cruzi-derived molecules such as GPI anchors and DNA induces proinflammatory cytokine production and host defense mechanisms. In this study, we demonstrate that DNA from T. cruzi stimulates cytokine production by APCs in a TLR9-dependent manner and synergizes with parasite-derived GPI anchor, a TLR2 agonist, in the induction of cytokines by macrophages. Compared with wild-type animals, T. cruzi-infected Tlr9−/− mice displayed elevated parasitemia and decreased survival. Strikingly, infected Tlr2−/−Tlr9−/− mice developed a parasitemia equivalent to animals lacking MyD88, an essential signaling molecule for most TLR, but did not show the acute mortality displayed by MyD88−/− animals. The enhanced susceptibility of Tlr9−/− and Tlr2−/−Tlr9−/− mice was associated with decreased in vivo IL-12/IFN-γ responses. Our results reveal that TLR2 and TLR9 cooperate in the control of parasite replication and that TLR9 has a primary role in the MyD88-dependent induction of IL-12/IFN-γ synthesis during infection with T. cruzi.

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Journal of Immunology

Tập 177 Số 6

3515-3519

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