Title: 1212 - Impaired STAT3-Mediated Immunity is Linked to Fungal and Bacterial Dysbiosis
Loreto Abusleme (Presenter)
Patricia Diaz, UConn Health
Alexandra Freeman, NIH
Teresa Wild, NIH
Laurie Brenchley, NIH
Jigar Desai, NIH
Wen-Ian Ng, NIH
Steven Holland, NIH
Michail Lionakis, NIH
Heidi Kong, NIH
Julia Segre, NIH
Niki Moutsopoulos, NIH
Objectives: Studies in individuals with rare monogenetic disorders can provide unique insights into the role of specific genes and pathways in human biology. In this regard, our work aimed to characterize the consequences of defective STAT3-mediated immunity on oral fungal and bacterial communities, through the study of patients with loss-of-function (LOF) STAT3 mutations (Autosomal-Dominant Hyper-IgE Syndrome; AD-HIES).
Methods: Medical/dental histories were recorded and intra-oral examinations were performed in a large cohort of AD-HIES patients (n=36). For corresponding microbiome studies in this population, oral mucosal samples were collected from patients and age/gender matched healthy controls. Microbiome samples were evaluated for fungal and bacterial community composition using high-throughput sequencing based on conserved phylogenetic markers. Real-time PCR assays were used to quantify relevant discriminatory taxa.
Results: Clinical evaluation of the AD-HIES cohort revealed a significant susceptibility to oral candidiasis, with 86% of patients reporting recurrent episodes. Analyses of oral fungal and bacterial communities demonstrated that AD-HIES patients harbor a distinct and less diverse microbiome to that of healthy controls. Comprehensive characterization of the oral mycobiome in AD-HIES patients with active candidiasis revealed a marked dominance of Candida, which upon speciation was identified as Candida albicans. In fact, we found a significant increase in C.albicans biomass in AD-HIES samples. LOF STAT3 was also associated with shifts in mucosal bacterial communities, which were characterized by increased abundance and biomass of streptococci (most notably Streptococcus oralis and Streptococcus mutans), particularly in the context of active C.albicans infection.
Conclusions: These studies document consequences of LOF STAT3 on oral mucosal immunity and microbiome, revealing a critical role for STAT3-mediated immunity in the containment of C.albicans as a commensal. Our data also suggests a synergistic inter-kingdom relationship between C.albicans and oral streptococci that may be a contributing factor for oral disease susceptibility.
This abstract is based on research that was funded entirely or partially by an outside source:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE