Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis
Loreto Abusleme, … , Heidi H. Kong, Niki M. Moutsopoulos
Loreto Abusleme, … , Heidi H. Kong, Niki M. Moutsopoulos
Published September 6, 2018
Citation Information: JCI Insight. 2018;3(17):e122061. https://doi.org/10.1172/jci.insight.122061.
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Research Article Infectious disease Microbiology

Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis

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.

Authors

Loreto Abusleme, Patricia I. Diaz, Alexandra F. Freeman, Teresa Greenwell-Wild, Laurie Brenchley, Jigar V. Desai, Weng-Ian Ng, Steven M. Holland, Michail S. Lionakis, Julia A. Segre, Heidi H. Kong, Niki M. Moutsopoulos

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Figure 2

Actively infected AD-HIES oral mucosal fungal communities are dominated by Candida albicans.

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Actively infected AD-HIES oral mucosal fungal communities are dominated ...
(A) Relative abundance plot depicts the major fungal taxa across communities in healthy controls (HC) and patients with AD-HIES. Patient groups shown are HC (n = 23 for tongue, n = 25 for buccal), uninfected AD-HIES (U_HIES, n = 9 for tongue and n = 8 for buccal), and actively infected HIES (A_HIES, n = 9 for tongue and n = 8 for buccal). Malassezia and Candida genera were further classified to species level due to abundance and clinical relevance. Each bar represents 1 subject. Empty bars represent missing samples. (B) Candida albicans genome copies per μg of DNA in tongue and buccal fungal communities from HC (n = 12 for tongue and n = 16 for buccal), uninfected (U_HIES, n = 8 for tongue and n = 7 for buccal), and actively infected (A_HIES, n = 7 for tongue and n = 7 for buccal) AD-HIES patients, quantified by real-time PCR. Candida albicans biomass values are expressed as log10 of genome copies. ****P < 0.0001 as determined by Kruskall-Wallis test and Dunn’s multiple comparisons test. Boxes extend from the 25th to 75th percentiles, and the whiskers were plotted from the minimum to maximum value. All outlying values were shown.