2006 Fiscal Year Final Research Report Summary
Analysis on regulatory mechanisms of inflammatory diseases and infectious diseases by innate immunity
| Project/Area Number |
17390144
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
TAKEDA Kiyoshi Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (20309446)
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| Project Period (FY) |
2005 – 2006
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| Keywords | innate immunity / Toll-like receptor / protozoan parasite / Trypanosoma cruzi / IFN-beta |
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| Research Abstract |
Host resistance to the intracellular protozoan parasite Trypanosoma cruzi depends on IFN-γ production by T cells and natural killer (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 Toll-like receptor (TLR)-dependent activation of innate immunity was abolished, were defective in the clearance of T cruzi, and showed impaired induction of IFN-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 anti-trypanosomal innate immune responses. MyD88-/-TRIF-/-and MyD88-/-IFNAR1-/-macrophages and DCs exhibited defective induction of the p47 GTPase IRG47 after T.cruzi infection. RNAi-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.
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Research Products
(12 results)
