Aberrant type 1 immunity drives susceptibility to mucosal fungal infections.
Science
; 371(6526)2021 01 15.
Article
em En
| MEDLINE
| ID: mdl-33446526
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Candida albicans
/
Candidíase Mucocutânea Crônica
/
Poliendocrinopatias Autoimunes
/
Imunidade nas Mucosas
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Animals
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Science
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos