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

Summary 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-γ (IFN-γ)-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-γ production whereas MyD88-independent signals promote Th1 differentiation in the lung.