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Science
Article
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Science
Article . 2021 . Peer-reviewed
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Science
Article . 2021
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Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

Authors: Marc Swidergall; Marc Swidergall; Muthulekha Swamydas; Nicolas Dutzan; Jean K. Lim; Mitsuru Matsumoto; Timothy J. Break; +37 Authors

Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

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

Keywords

Male, T-Lymphocytes, Mice, Receptors, Candida albicans, Medicine and Health Sciences, 2.1 Biological and endogenous factors, Aetiology, Polyendocrinopathies, Autoimmune, Immunologic Surveillance, Inbred BALB C, Mucosal, Mice, Inbred BALB C, Interleukin-17, Candidiasis, Chronic Mucocutaneous, Candidiasis, Life Sciences, Middle Aged, Infectious Diseases, STAT1 Transcription Factor, Female, Infection, Genomics and Computational Biology Core, Adult, Adolescent, General Science & Technology, 610, Chronic Mucocutaneous, Autoimmune Disease, Young Adult, Interferon-gamma, Animals, Humans, Immunity, Mucosal, JMG, Aged, Janus Kinases, Animal, Inflammatory and immune system, Interleukins, Immunity, Mouth Mucosa, Disease Models, Animal, Emerging Infectious Diseases, Polyendocrinopathies, Disease Models, Autoimmune

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
130
Top 1%
Top 10%
Top 1%
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bronze