Commensal Candida albicans Positively Calibrates Systemic Th17 Immunological Responses

Summary Mucosal barriers are densely colonized by pathobiont microbes such as Candida albicans , capable of invasive disseminated infection. However, systemic infections occur infrequently in healthy individuals, suggesting that pathobiont commensalismmay elicit host benefits. We show that intestinal colonization with C. albicansdrives systemic expansion of fungal-specific Th17 CD4 + T cells and IL-17 responsiveness by circulating neutrophils, which synergistically protect against C. albicansinvasive infection. Protection conferred by commensal C. albicansrequires persistent fungal colonization and extends to other extracellular invasive pathogens such as Staphylococcus aureus . However, commensal C. albicansdoes not protect against intracellular influenza virus infection and exacerbates allergic airway inflammation susceptibility, indicating that positively calibrating systemic Th17 responses is not uniformly beneficial. Thus, systemic Th17 inflammation driven by CD4 + T cells responsive to tonic stimulation by commensal C. albicansimproves host defense against extracellular pathogens, but with potentially harmful immunological consequences.