Lymphocyte depletion after alemtuzumab induction disrupts intestinal fungal microbiota in cynomolgus monkeys.

Abstract

The interactions of specific fungal phylotypes with immune cells have been recently documented; however, little is known whether gut fungal microbiota is influenced by aberrant immune response in immunosuppressive state. This study aimed to define the biologic impact of lymphocyte depletion on gut fungal microbiota and their relationship. Fifteen male cynomolgus monkeys with CD52 antigen negative on erythrocytes were administered intravenously with a single dose (3.0 mg kg body weight) of alemtuzumab. Depletion and repopulation of circulating and mucosal lymphocytes were determined. The dynamic variations of intestinal fungal microbiota were characterized using 18S ribosomal DNA-based molecular techniques. The fungal microbiota in colonal mucosa was perturbed during lymphocyte depletion, characterized by increased diversity and colonization of Candida albicans, Aspergillus clavatus, and Saccharomyces cerevisiae. The diversity of the fecal fungal population decreased markedly after mucosal lymphocyte depletion, and specific fungal phylotypes, especially Candida albicans, Saccharomyces cerevisiae, and Botryotinia fuckeliana, were expanded (P<0.05). After reconstitution of mucosal lymphocytes, the composition and diversity of the gut fungal microbiota were both recovered. A close association of the community diversity and Candida albicans colonization with T lymphocyte subsets was also identified. Our findings demonstrate that mucosal lymphocyte depletion leads to the dysbiosis of gut fungal microbiota, suggesting its role in maintaining host-fungus homeostasis. The pathophysiologic consequences of this altered fungal colonization might provide novel clues to uncover the underlying mechanism of enteric fungal infection in immunosuppressive therapies.