Aberrant type 1 immunity drives susceptibility to mucosal fungal infections-Reference-Cited by-同舟云学术

Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

Published:2021-01-15 Issue:6526 Volume:371 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Break Timothy J.¹^ORCID,Oikonomou Vasileios¹^ORCID,Dutzan Nicolas²^ORCID,Desai Jigar V.¹^ORCID,Swidergall Marc³⁴^ORCID,Freiwald Tilo⁵^ORCID,Chauss Daniel⁵,Harrison Oliver J.⁶^ORCID,Alejo Julie⁷,Williams Drake W.²^ORCID,Pittaluga Stefania⁷^ORCID,Lee Chyi-Chia R.⁷^ORCID,Bouladoux Nicolas⁶^ORCID,Swamydas Muthulekha¹^ORCID,Hoffman Kevin W.⁸^ORCID,Greenwell-Wild Teresa²,Bruno Vincent M.⁹^ORCID,Rosen Lindsey B.¹⁰^ORCID,Lwin Wint¹¹,Renteria Andy¹^ORCID,Pontejo Sergio M.¹²^ORCID,Shannon John P.¹³^ORCID,Myles Ian A.¹⁴^ORCID,Olbrich Peter¹⁰^ORCID,Ferré Elise M. N.¹^ORCID,Schmitt Monica¹,Martin Daniel¹⁵^ORCID,Barber Daniel L.¹⁶^ORCID,Solis Norma V.³,Notarangelo Luigi D.¹⁷^ORCID,Serreze David V.¹⁸^ORCID,Matsumoto Mitsuru¹⁹,Hickman Heather D.¹³^ORCID,Murphy Philip M.¹²^ORCID,Anderson Mark S.¹¹^ORCID,Lim Jean K.⁸^ORCID,Holland Steven M.¹⁰^ORCID,Filler Scott G.³⁴^ORCID,Afzali Behdad⁵^ORCID,Belkaid Yasmine⁶^ORCID,Moutsopoulos Niki M.²^ORCID,Lionakis Michail S.¹^ORCID,

Affiliation:

1. Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.

2. Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA.

3. Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

4. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

5. Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA.

6. Metaorganism Immunity Section, Laboratory of Immune System Biology, NIAID, Bethesda, MD, USA.

7. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA.

8. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

9. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

10. Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD, USA.

11. Diabetes Center, University of California, San Francisco, CA, USA.

12. Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, Bethesda, MD, USA.

13. Viral Immunity and Pathogenesis Unit, LCIM, NIAID, Bethesda, MD, USA.

14. Epithelial Therapeutics Unit, LCIM, NIAID, Bethesda, MD, USA.

15. Genomics and Computational Biology Core, NIDCR, Bethesda, MD, USA.

16. T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, NIAID, Bethesda, MD, USA.

17. Immune Deficiency Genetics Section, LCIM, NIAID, Bethesda, MD, USA.

18. Jackson Laboratory, Bar Harbor, ME, USA.

19. Division of Molecular Immunology, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.

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

Funder

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference74 articles.

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