TLR-dependent induction of IFN-β mediates host defense against Trypanosoma cruzi

Ritsuko Koga, Shinjiro Hamano, Hirotaka Kuwata, Koji Atarashi, Masahiro Ogawa, Hajime Hisaeda, Masahiro Yamamoto, Shizuo Akira, Kunisuke Himeno, Makoto Matsumoto, Kiyoshi Takeda

研究成果: Article査読

74 被引用数 (Scopus)


Host resistance to the intracellular protozoan parasite Trypanosoma cruzi depends on IFN-γ production by T cells and NK cells. However, the involvement of innate immunity in host resistance to T. cruzi remains unclear. In the present study, we investigated host defense against T. cruzi by focusing on innate immunity. Macrophages and dendritic cells (DCs) from MyD88 -/-TRIF-/- mice, in which TLR-dependent activation of innate immunity was abolished, were defective in the clearance of T. cruzi and showed impaired induction of TFN-β during T. cruzi infection. Neutralization of IFN-β in MyD88-/- macrophages led to enhanced T. cruzi growth. Cells from MyD88-/-IFNAR1-/- mice also showed impaired T. cruzi clearance. Furthermore, both MyD88 -/-TRIF-/- and MyD88-/-IFNAR1-/- mice were highly susceptible to in vivo T. cruzi infection, highlighting the involvement of innate immune responses in T. cruzi infection. We further analyzed the molecular mechanisms for the IFN-β-mediated antitrypanosomal innate immune responses. MyD88-/-TRIF-/- and MyD88 -/-IFNAR1-/- macrophages and DCs exhibited defective induction of the GTPase IFN-inducible p47 (IRG47) after T. cruzi infection. RNA interference-mediated reduction of IRG47 expression in MyD88-/- macrophages resulted in increased intracellular growth of T. cruzi. These findings suggest that TLR-dependent expression of IFN-β is involved in resistance to T. cruzi infection through the induction of IRG47.

ジャーナルJournal of Immunology
出版ステータスPublished - 2006 11月 15

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学


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