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Aberrant type 1 immunity drives susceptibility to mucosal fungal infections.

Science (New York, N.Y.) (2021-01-16)
Timothy J Break, Vasileios Oikonomou, Nicolas Dutzan, Jigar V Desai, Marc Swidergall, Tilo Freiwald, Daniel Chauss, Oliver J Harrison, Julie Alejo, Drake W Williams, Stefania Pittaluga, Chyi-Chia R 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 Schmitt, Daniel Martin, Daniel L Barber, Norma V Solis, Luigi D Notarangelo, David V 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
RÉSUMÉ

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.

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3,3′-Diaminobenzidine tetrahydrochloride, tablet, 10 mg substrate per tablet
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Essai de perméabilité vasculaire in vitro (24 puits), This In Vitro Vascular Permeability Assay kit employs a 24-well plate and provides an efficient system for evaluating the effects of chemicals & drug compounds on endothelial cell adsorption, transport & permeability.
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Anti-IL-17 (ab2) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution