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

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7059-7066
Number of pages8
JournalJournal of Immunology
Volume177
Issue number10
Publication statusPublished - 2006 Nov 15

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Koga, R., Hamano, S., Kuwata, H., Atarashi, K., Ogawa, M., Hisaeda, H., Yamamoto, M., Akira, S., Himeno, K., Matsumoto, M., & Takeda, K. (2006). TLR-dependent induction of IFN-β mediates host defense against Trypanosoma cruzi. Journal of Immunology, 177(10), 7059-7066.