Aberrant type 1 immunity drives susceptibility to mucosal fungal infections
Aberrant type 1 immunity drives susceptibility to mucosal fungal infections
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
- University of Perugia Italy
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH
- University of California, Los Angeles United States
- National Institutes of Health United States
- National Institute of Allergy and Infectious Diseases United States
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
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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