Rivera Amariliz, Ro Grace, Van Epps Heather L, Simpson Tyler, Leiner Ingrid, Sant'Angelo Derek B, Pamer Eric G
Infectious Diseases Service, Immunology Program, Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 9, New York, New York 10021, USA.
Immunity. 2006 Oct;25(4):665-75. doi: 10.1016/j.immuni.2006.08.016. Epub 2006 Oct 5.
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.
烟曲霉是一种可引发一系列疾病的霉菌，包括免疫功能低下人群的致命肺部感染以及特应性个体的过敏性哮喘。辅助性T细胞1（Th1）CD4(+) T细胞可抵御侵袭性烟曲霉感染，而Th2 CD4(+) T细胞在吸入烟曲霉孢子后会加重哮喘症状。在此，我们证明，烟曲霉特异性T细胞在引流肺部的淋巴结中迅速启动，并在抵达气道后完全分化为产生干扰素-γ（IFN-γ）的Th1 CD4(+) T细胞。在引流淋巴结中，髓样分化因子88（MyD88）介导的信号增强了烟曲霉特异性CD4(+) T细胞中T盒转录因子（T-bet）的诱导，但气道中的T细胞增殖、迁移和Th1分化与Toll样受体（TLR）和MyD88无关。我们的研究表明，呼吸道真菌感染期间CD4(+) T细胞的分化是渐进性的，淋巴结中TLR介导的信号增强了产生IFN-γ的潜力，而MyD88非依赖性信号促进了肺部的Th1分化。
