@article{651b1a285ce24f19a28580eee0e7afb5,
title = "Aberrant type 1 immunity drives susceptibility to mucosal fungal infections",
abstract = "Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with AIRE deficiency, an autoimmune disease characterized by selective susceptibility to mucosal but not systemic fungal infection, mucosal type 17 responses are intact while type 1 responses are exacerbated. These responses promote aberrant interferon-γ (IFN-γ)- and signal transducer and activator of transcription 1 (STAT1)-dependent epithelial barrier defects as well as mucosal fungal infection susceptibility. Concordantly, genetic and pharmacologic inhibition of IFN-γ or Janus kinase (JAK)-STAT signaling ameliorates mucosal fungal disease. Thus, we identify aberrant T cell-dependent, type 1 mucosal inflammation as a critical tissue-specific pathogenic mechanism that promotes mucosal fungal infection susceptibility in mice and humans.",
author = "{Genomics and Computational Biology Core} and Break, {Timothy J.} and Vasileios Oikonomou and Nicolas Dutzan and Desai, {Jigar V.} and Marc Swidergall and Tilo Freiwald and Daniel Chauss and Harrison, {Oliver J.} and Julie Alejo and Williams, {Drake W.} and Stefania Pittaluga and Lee, {Chyi Chia R.} and Nicolas Bouladoux and Muthulekha Swamydas and Hoffman, {Kevin W.} and Teresa Greenwell-Wild and Bruno, {Vincent M.} and Rosen, {Lindsey B.} and Wint Lwin and Andy Renteria and Pontejo, {Sergio M.} and Shannon, {John P.} and Myles, {Ian A.} and Peter Olbrich and Ferr{\'e}, {Elise M.N.} and Monica Schmitt and Daniel Martin and Barber, {Daniel L.} and Solis, {Norma V.} and Notarangelo, {Luigi D.} and Serreze, {David V.} and Mitsuru Matsumoto and Hickman, {Heather D.} and Murphy, {Philip M.} and Anderson, {Mark S.} and Lim, {Jean K.} and Holland, {Steven M.} and Filler, {Scott G.} and Behdad Afzali and Yasmine Belkaid and Moutsopoulos, {Niki M.} and Lionakis, {Michail S.}",
note = "Funding Information: Supported by the NIAID Division of Intramural Research (M.S.L., Y.B., S.M.H., P.M.M., H.D.H., L.D.N., D.L.B., and I.A.M.); the NIDCR Division of Intramural Research (N.M.M.); the NCI Division of Intramural Research (S.P. and C.-C.R.L.); the NIDDK Division of Intramural Research (B.A.); NIDCD Division of Intramural Research grant ZIC DC000086 to the Genomics and Computational Biology Core; NIH grants R01DE022600 and R01AI124566 (S.G.F.); NIH grant R00DE026856 (Ma.S.); Deutsche Forschungsgemeinschaft research fellowship FR 3851/2-1 (T.F.); Juan Rodes program grant JR 18/00042 (P.O.); Instituto de Salud Carlos III, Madrid; Consejer{\'i}a de Salud y Familias de Andalucia grant EF-0038-2016; Estancias Formativas de Larga Duraci{\'o}n; and the Asociaci{\'o}n de Pediatr{\'i}a (Beca para Estancias de Larga Duraci{\'o}n), Madrid. Publisher Copyright: {\textcopyright} 2021 The Authors, some rights reserved.",
year = "2021",
month = jan,
day = "15",
doi = "10.1126/science.aay5731",
language = "English",
volume = "371",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6526",
}