title: IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance.
abstract: Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. We found here that the IL-23/IL-17 developmental pathway acted as a negative regulator of the Th1-mediated immune resistance to fungi and played an inflammatory role previously attributed to uncontrolled Th1 cell responses. Both inflammation and infection were exacerbated by a heightened Th17 response against Candida albicans and Aspergillus fumigatus, two major human fungal pathogens. IL-23 acted as a molecular connection between uncontrolled fungal growth and inflammation, being produced by dendritic cells in response to a high fungal burden and counter-regulating IL-12p70 production. Both IL-23 and IL-17 subverted the inflammatory program of neutrophils, which resulted in severe tissue inflammatory pathology associated with infection. Our data are the first demonstrating that the IL-23/IL-17 pathway promotes inflammation and susceptibility in an infectious disease model. As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi.
authors: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors: Teresa
authors: T
authors: Zelante
authors: Antonella
authors: A
authors: De Luca
authors: Pierluigi
authors: P
authors: Bonifazi
authors: Claudia
authors: C
authors: Montagnoli
authors: Silvia
authors: S
authors: Bozza
authors: Silvia
authors: S
authors: Moretti
authors: Maria L
authors: ML
authors: Belladonna
authors: Carmine
authors: C
authors: Vacca
authors: Carmela
authors: C
authors: Conte
authors: Paolo
authors: P
authors: Mosci
authors: Francesco
authors: F
authors: Bistoni
authors: Paolo
authors: P
authors: Puccetti
authors: Robert A
authors: RA
authors: Kastelein
authors: Manfred
authors: M
authors: Kopf
authors: Luigina
authors: L
authors: Romani
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000502:physiology*; D053759:Interleukin-23 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23