Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis

被引：51

作者：

Abusleme, Loreto ^{[1
,2
]}

Diaz, Patricia I. ^{[3
]}

Freeman, Alexandra F. ^{[4
]}

Greenwell-Wild, Teresa ^{[1
]}

Brenchley, Laurie ^{[1
]}

Desai, Jigar V. ^{[5
]}

Ng, Weng-Ian ^{[6
]}

Holland, Steven M. ^{[4
]}

Lionakis, Michail S. ^{[5
]}

Segre, Julia A. ^{[6
]}

Kong, Heidi H. ^{[7
]}

Moutsopoulos, Niki M. ^{[1
]}

机构：

[1] NIH, NIDCR, Oral Immun & Inflammat Unit, Bldg 10, Bethesda, MD 20892 USA

[2] Univ Chile, Fac Dent, Santiago, Chile

[3] UConn Hlth Ctr, Div Periodontol, Dept Oral Hlth & Diagnost Sci, Farmington, CT USA

[4] NIAID, LCIM, 9000 Rockville Pike, Bethesda, MD 20892 USA

[5] NIAID, Fungal Pathogenesis Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA

[6] NHGRI, Microbial Genom Sect, Bldg 10, Bethesda, MD 20892 USA

[7] NIAMS, Cutaneous Microbiome & Inflammat Sect, NIH, Bethesda, MD USA

来源：

JCI INSIGHT | 2018年 / 3卷 / 17期

关键词：

HYPER-IGE SYNDROME; CHRONIC MUCOCUTANEOUS CANDIDIASIS; EARLY-CHILDHOOD CARIES; TH17; CELLS; HUMAN SKIN; PRIMARY IMMUNODEFICIENCIES; OROPHARYNGEAL CANDIDIASIS; STREPTOCOCCUS-MUTANS; EPITHELIAL-CELLS; HUMAN MICROBIOME;

D O I：

10.1172/jci.insight.122061

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：13

共 73 条

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