Innate immune activation and CD4+ T cell priming during respiratory fungal infection

被引:117
作者
Rivera, Amariliz [1 ]
Ro, Grace [1 ]
Van Epps, Heather L. [1 ]
Simpson, Tyler [1 ]
Leiner, Ingrid [1 ]
Sant'Angelo, Derek B. [1 ]
Pamer, Eric G. [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Infect Dis Serv, Program Immunol, New York, NY 10021 USA
关键词
D O I
10.1016/j.immuni.2006.08.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Aspergillus fumigatus is a mold that causes a spectrum of diseases, including lethal lung infections in immunocompromised humans and allergic asthma in atopic individuals. T helper 1 (Th1) CD4(+)T cells protect against invasive A. fumigatus infections whereas Th2 CD4(+) T cells exacerbate asthma upon inhalation of A. fumigatus spores. Herein, we demonstrate that A. fumigatus-specific T cells were rapidly primed in lymph nodes draining the lung and fully differentiated into interferon-gamma (IFN-gamma)-producing Th1 CD4(+) T cells upon arrival in the airways. T-bet induction in A. fumigatus-specific CD4(+) T cells was enhanced by MyD88-mediated signals in draining lymph nodes, but T cell proliferation, trafficking, and Th1 differentiation in the airways were Toll-like receptor (TLR) and MyD88 independent. Our studies demonstrate that CD4(+) T cell differentiation during respiratory fungal infection occurs incrementally, with TLR-mediated signals in the lymph node enhancing the potential for IFN-gamma production whereas MyD88-independent signals promote Th1 differentiation in the lung.
引用
收藏
页码:665 / 675
页数:11
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