Aberrant tissue localization of fungus-specific CD4+ T cells in IL-10-deficient mice.
Aspergillus fumigatus, a common environmental fungus, can cause lethal invasive infections in immunocompromised hosts. In immunocompetent individuals, however, inhaled A. fumigatus spores prime CD4(+) T cells and activate immune responses that prevent invasive infection. Calibration of inflammatory responses to levels that prevent fungal invasion without inducing collateral tissue damage is essential for host survival, but the underlying regulatory mechanisms remain undefined. Although IL-10 is a validated regulatory cytokine that suppresses immune responses, and IL-10 deficiency or blockade generally enhances immune responses, we find that A. fumigatus-specific T cell frequencies are markedly reduced in airways of IL-10-deficient mice. T cell priming, proliferation, and survival were unaffected by IL-10 deficiency and did not account for decreased frequencies of A. fumigatus-specific T cells in the airways of IL-10-deficient mice. Instead, IL-10 deficiency results in redistribution of A. fumigatus-specific T cells from infected lungs to the gut, a process that is reversed by antibiotic-mediated depletion of intestinal microbes. Our studies demonstrate that disregulated immune responses in the gut can result in dramatic redistribution of pathogen-specific T cells within the host.
Rivera
Amariliz
A
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Collins
Nichole
N
Stephan
Matthias T
MT
Lipuma
Lauren
L
Leiner
Ingrid
I
Pamer
Eric G
EG
D000818:Animals; D001228:Aspergillosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
D018984:Epitopes, T-Lymphocyte; D016753:Interleukin-10