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JCI Insight. 2018 Sep 6;3(17). pii: 122061. doi: 10.1172/jci.insight.122061. eCollection 2018 Sep 6.

Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis.

Author information

1
Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, Maryland, USA.
2
Faculty of Dentistry, University of Chile, Santiago, Chile.
3
Division of Periodontology, Department of Oral Health and Diagnostic Sciences, UConn Health Center, Farmington, Connecticut, USA.
4
Laboratory of Clinical Immunology and Microbiology (LCIM).
5
Fungal Pathogenesis Section, NIAID.
6
Microbial Genomics Section, NHGRI, and.
7
Cutaneous Microbiome and Inflammation Section, NIAMS, NIH, Bethesda, Maryland, USA.

Abstract

Studies in patients with genetic defects can provide unique insights regarding the role of specific genes and pathways in humans. Patients with defects in the Th17/IL-17 axis, such as patients harboring loss-of-function STAT3 mutations (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral fungal infections. Our studies aimed to comprehensively evaluate consequences of STAT3 deficiency on the oral commensal microbiome. We characterized fungal and bacterial communities in AD-HIES in the presence and absence of oral fungal infection compared with healthy volunteers. Analyses of oral mucosal fungal communities in AD-HIES revealed severe dysbiosis with dominance of Candida albicans (C. albicans) in actively infected patients and minimal representation of health-associated fungi and/or opportunists. Bacterial communities also displayed dysbiosis in AD-HIES, particularly in the setting of active Candida infection. Active candidiasis was associated with decreased microbial diversity and enrichment of the streptococci Streptococcus oralis (S. oralis) and S. mutans, suggesting an interkingdom interaction of C. albicans with oral streptococci. Increased abundance of S. mutans was consistent with susceptibility to dental caries in AD-HIES. Collectively, our findings illustrate a critical role for STAT3/Th17 in the containment of C. albicans as a commensal organism and an overall contribution in the establishment of fungal and bacterial oral commensal communities.

KEYWORDS:

Fungal infections; Infectious disease; Microbiology; Monogenic diseases

PMID:
30185668
PMCID:
PMC6171814
DOI:
10.1172/jci.insight.122061
[Indexed for MEDLINE]
Free PMC Article

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