IL-17 and therapeutic kynurenines in pathogenic inflammation to fungi.
Largely viewed as proinflammatory, innate responses combine with adaptive immunity to generate the most effective form of antifungal resistance, and T cells exercise feedback control over diverse effects of inflammation on infection. Some degree of inflammation is required for protection, particularly in mucosal tissues, during the transitional response occurring between the rapid innate and slower adaptive response. However, progressive inflammation worsens disease and ultimately prevents pathogen eradication. IDO, tryptophan catabolites ("kynurenines"), and regulatory T cells help to tame overzealous and exaggerated inflammatory responses. In this context, IL-23 and the Th17 pathway, which down-regulate tryptophan catabolism, may instead favor pathology and serve to accommodate the seemingly paradoxical association of chronic inflammation with fungal persistence. Recent data support a view in which IL-23/IL-17 antagonistic strategies, including the administration of synthetic kynurenines, could represent a new means of harnessing progressive or potentially harmful inflammation.
Romani
Luigina
L
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy. lromani@unipg.it
Zelante
Teresa
T
De Luca
Antonella
A
Fallarino
Francesca
F
Puccetti
Paolo
P
D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005658:Fungi / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D007737:Kynurenine / Q000276:immunology / Q000378:metabolism*; D009181:Mycoses / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D014364:Tryptophan / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020381:Interleukin-17; D053759:Interleukin-23; D007737:Kynurenine; D014364:Tryptophan