Immunity and Tolerance to Aspergillus Involve Functionally Distinct Regulatory T Cells and Tryptophan Catabolism

摘要: The inherent resistance to diseases caused by Aspergillus fumigatus suggests the occurrence of regulatory mechanisms that provide host with adequate defense without necessarily eliminating fungus or causing unacceptable levels damage. In this study, we show a division labor occurs between functionally distinct T cells (Treg) are coordinately activated CD28/B-7-dependent costimulatory pathway after exposure mice conidia. Early in infection, inflammation is controlled expansion, activation and local recruitment CD4+CD25+ Treg capable suppressing neutrophils through combined actions IL-10 CTLA-4 on indoleamine 2,3-dioxygenase. IFN-gamma produced early phase set subsequent adaptive stage conditioning 2,3-dioxygenase-dependent tolerogenic program dendritic expansion Treg, which produce TGF-beta, inhibit Th2 cells, prevent allergy fungus. coordinate may, however, be subverted fungus, as germinating conidia interfering anti-inflammatory programs. Thus, regulation an essential component response infection its manipulation may allow pathogen overcome promote disease.