Intestinal and skin colonization by Candida albicanscontributes to disrupted regulatory T cells in early life.

Abstract Perturbations of the mucosal immune system and the microbiota can lead to allergic disorders with a lifelong impact. With up to 90% of cases diagnosed by age 6, atopic dermatitis represents a unique allergic disorder during early life. Diagnosis of atopic dermatitis is associated with an increased risk for other allergic disorders throughout life. The opportunistic fungal species Candida albicansis often found as part of a dysbiotic microbiota and its presence is associated with increased risk of atopy. While adult mice are unable to be stably colonized with C. albicanswithout the use of antibiotics, we have found that mice exposed to C. albicansprior to weaning maintain long term colonization in the gut and on the skin. In mice colonized in early life with C. albicansin the GI tract, FoxP3+ T cells were significantly decreased post-weaning in the mesenteric lymph node as well as in the small intestine and colon lamina propria. Colonization by C. albicansresulted in an increased Th17 response, with increased RORγt+ and c-Maf+ T cells in the colon lamina propria. In a clinical observation study, we found C. albicanscolonization in the intestine of prematurely born infants, suggesting colonization of the human GI tract with C. albicansmay frequently occur. As the microbiota develops with age, the presence of C. albicansmay impact the normal course of increasing complexity and diversity in this ecosystem. The establishment of regulatory T cells in early life is vital to maintaining tolerance to commensal organisms throughout life; this disruption in regulatory T cells potentially links colonization by C. albicansto the development of atopy and allergic responses. Supported by grants from Mayo Clinic Center for Individualized Medicine