Aberrant type 1 immunity drives susceptibility to mucosal fungal infections
Timothy J. Break, Vasileios Oikonomou, Nicolás Dutzan, Jigar V. Desai, Marc Swidergall, Tilo Freiwald, Daniel Chauss, Oliver J. Harrison, Julie Alejo, D. Williams, Stefania Pittaluga, Chyi‐Chia Richard Lee, Nicolas Bouladoux, Muthulekha Swamydas, Kevin W. Hoffman, Teresa Greenwell‐Wild, Vincent M. Bruno, Lindsey B. Rosen, Wint Lwin, Andy Renteria, Sergio M. Pontejo, John P. Shannon, Ian A. Myles, Peter Olbrich, Elise M. N. Ferré, Monica M. Schmitt, Daniel Martı́n, Genomics and Computational Biology Core, Daniel L. Barber, Norma V. Solis, Luigi D. Notarangelo, David Serreze, Mitsuru Matsumoto, Heather D. Hickman, Philip M. Murphy, Mark S. Anderson, Jean K. Lim, Steven M. Holland, Scott G. Filler, Behdad Afzali, Yasmine Belkaid, Niki M. Moutsopoulos, Michail S. Lionakis
Abstract
Type 1 immunity gives fungi a foothold Type 17 immune responses play a vital role against fungal infections of the mucosa. It remains unclear whether other types of immune responses can also contribute to host defense against these pathogens. The yeast Candida albicans prominently infects patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), an inherited disease caused by loss-of-function mutations in the AIRE gene. Break et al. report that the oral susceptibility of Aire -deficient mice to C. albicans is not due to aberrant type 17 responses. Rather, the overproduction of interferon-γ by local CD4 + and CD8 + T cells in these mice disrupts the epithelial barrier, which increases susceptibility to C. albicans invasion. Similar type 1 immune pathways are operational in APECED patients. Inhibition of interferon-γ or the JAK-STAT signaling pathway in mice ameliorates disease symptoms, suggesting potential future therapeutic interventions for certain classes of fungal disease. Science , this issue p. eaay5731