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Aberrant type 1 immunity drives susceptibility to mucosal fungal infections.
Break, Timothy J; Oikonomou, Vasileios; Dutzan, Nicolas; Desai, Jigar V; Swidergall, Marc; Freiwald, Tilo; Chauss, Daniel; Harrison, Oliver J; Alejo, Julie; Williams, Drake W; Pittaluga, Stefania; Lee, Chyi-Chia R; Bouladoux, Nicolas; Swamydas, Muthulekha; Hoffman, Kevin W; Greenwell-Wild, Teresa; Bruno, Vincent M; Rosen, Lindsey B; Lwin, Wint; Renteria, Andy; Pontejo, Sergio M; Shannon, John P; Myles, Ian A; Olbrich, Peter; Ferré, Elise M N; Schmitt, Monica; Martin, Daniel; Barber, Daniel L; Solis, Norma V; Notarangelo, Luigi D; Serreze, David V; Matsumoto, Mitsuru; Hickman, Heather D; Murphy, Philip M; Anderson, Mark S; Lim, Jean K; Holland, Steven M; Filler, Scott G; Afzali, Behdad; Belkaid, Yasmine; Moutsopoulos, Niki M; Lionakis, Michail S.
Afiliación
  • Break TJ; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
  • Oikonomou V; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
  • Dutzan N; Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA.
  • Desai JV; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
  • Swidergall M; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Freiwald T; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Chauss D; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA.
  • Harrison OJ; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA.
  • Alejo J; Metaorganism Immunity Section, Laboratory of Immune System Biology, NIAID, Bethesda, MD, USA.
  • Williams DW; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA.
  • Pittaluga S; Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA.
  • Lee CR; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA.
  • Bouladoux N; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA.
  • Swamydas M; Metaorganism Immunity Section, Laboratory of Immune System Biology, NIAID, Bethesda, MD, USA.
  • Hoffman KW; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
  • Greenwell-Wild T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bruno VM; Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA.
  • Rosen LB; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Lwin W; Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD, USA.
  • Renteria A; Diabetes Center, University of California, San Francisco, CA, USA.
  • Pontejo SM; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
  • Shannon JP; Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, Bethesda, MD, USA.
  • Myles IA; Viral Immunity and Pathogenesis Unit, LCIM, NIAID, Bethesda, MD, USA.
  • Olbrich P; Epithelial Therapeutics Unit, LCIM, NIAID, Bethesda, MD, USA.
  • Ferré EMN; Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD, USA.
  • Schmitt M; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
  • Martin D; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
  • Solis NV; T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, NIAID, Bethesda, MD, USA.
  • Notarangelo LD; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Serreze DV; Immune Deficiency Genetics Section, LCIM, NIAID, Bethesda, MD, USA.
  • Matsumoto M; Jackson Laboratory, Bar Harbor, ME, USA.
  • Hickman HD; Division of Molecular Immunology, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.
  • Murphy PM; Viral Immunity and Pathogenesis Unit, LCIM, NIAID, Bethesda, MD, USA.
  • Anderson MS; Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, Bethesda, MD, USA.
  • Lim JK; Diabetes Center, University of California, San Francisco, CA, USA.
  • Holland SM; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Filler SG; Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD, USA.
  • Afzali B; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Belkaid Y; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Moutsopoulos NM; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA.
  • Lionakis MS; Metaorganism Immunity Section, Laboratory of Immune System Biology, NIAID, Bethesda, MD, USA.
Science ; 371(6526)2021 01 15.
Article en En | MEDLINE | ID: mdl-33446526
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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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Candida albicans / Candidiasis Mucocutánea Crónica / Poliendocrinopatías Autoinmunes / Inmunidad Mucosa Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Science Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Candida albicans / Candidiasis Mucocutánea Crónica / Poliendocrinopatías Autoinmunes / Inmunidad Mucosa Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Science Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos