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- Title
IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance.
- Authors
Zelante, Teresa; De Luca, Antonella; Bonifazi, Pierluigi; Montagnoli, Claudia; Bozza, Silvia; Moretti, Silvia; Belladonna, Maria L.; Vacca, Carmine; Conte, Carmela; Mosci, Paolo; Bistoni, Francesco; Puccetti, Paolo; Kastelein, Robert A.; Kopf, Manfred; Romani, Luigina
- 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. See accompanying commentary:
- Publication
European Journal of Immunology, 2007, Vol 37, Issue 10, p2695
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200737409