Controlling pathogenic inflammation to fungi.
The balance between pro- and anti-inflammatory signaling is a prerequisite for successful host-fungal interactions. Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases and limit protective, antifungal immune responses. The newly described Th17 developmental pathway may play an inflammatory role previously attributed to uncontrolled Th1 cell responses. The capacity of regulatory T cells to inhibit aspects of innate and adaptive antifungal immunity, including functional Th17 antagonism, is required for protective tolerance to fungi. Indoleamine 2,3-dioxygenase and tryptophan catabolites contribute to such a homeostatic condition by providing the host with immune defense mechanisms adequate for protection, without necessarily eliminating fungal pathogens - which would impair immune memory - or causing an unacceptable level of tissue damage. These new findings provide a molecular connection between the failure to resolve inflammation and lack of antifungal immune resistance, and point to strategies for immune therapy of fungal infections that attempt to limit inflammation in order to stimulate an effective immune response.
Romani
Luigina
L
University of Perugia, Department of Experimental Medicine and Biochemical Sciences, Via del Giochetto, 06122 Perugia, Italy. lromani@unipg.it
Puccetti
Paolo
P
D000818:Animals; D005658:Fungi / Q000276:immunology*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007113:Immunity, Innate; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D009181:Mycoses / Q000276:immunology / Q000473:pathology*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D053450:Glucocorticoid-Induced TNFR-Related Protein; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020381:Interleukin-17; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D014364:Tryptophan