TY - JOUR
T1 - TLR-dependent induction of IFN-β mediates host defense against Trypanosoma cruzi
AU - Koga, Ritsuko
AU - Hamano, Shinjiro
AU - Kuwata, Hirotaka
AU - Atarashi, Koji
AU - Ogawa, Masahiro
AU - Hisaeda, Hajime
AU - Yamamoto, Masahiro
AU - Akira, Shizuo
AU - Himeno, Kunisuke
AU - Matsumoto, Makoto
AU - Takeda, Kiyoshi
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2006/11/15
Y1 - 2006/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33750833949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750833949&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.10.7059
DO - 10.4049/jimmunol.177.10.7059
M3 - Article
C2 - 17082622
AN - SCOPUS:33750833949
SN - 0022-1767
VL - 177
SP - 7059
EP - 7066
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -