Innate immune activation and CD4+ T cell priming during respiratory fungal infection.
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.
Rivera
Amariliz
A
Infectious Diseases Service, Immunology Program, Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 9, New York, New York 10021, USA.
Ro
Grace
G
Van Epps
Heather L
HL
Simpson
Tyler
T
Leiner
Ingrid
I
Sant'Angelo
Derek B
DB
Pamer
Eric G
EG
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D001228:Aspergillosis / Q000235:genetics / Q000276:immunology*; D001232:Aspergillus fumigatus; D002465:Cell Movement; D049109:Cell Proliferation; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D008172:Lung Diseases, Fungal / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88; D018417:Th1 Cells / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D007371:Interferon-gamma