Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria

Summary Commensalintestinal microbes are collectively beneficial in preventing local tissue injury and augmenting systemic antimicrobial immunity. However, given the near-exclusive focus on bacterial species in establishing these protective benefits, the contributions of other types of commensalmicrobes remain poorly defined. Here, we show that commensalfungi can functionally replace intestinal bacteria by conferring protection against injury to mucosal tissues and positively calibrating the responsiveness of circulating immune cells. Susceptibility to colitis and influenzaA virusinfection occurring upon commensalbacteria eradication is efficiently overturned by mono-colonization with either Candida albicans or Saccharomyces cerevisiae . The protective benefits of commensalfungi are mediated by mannans, a highly conserved component of fungal cell walls, since intestinal stimulation with this moiety alone overrides disease susceptibility in mice depleted of commensalbacteria. Thus, commensalenteric fungi safeguard local and systemic immunity by providing tonic microbial stimulation that can functionally replace intestinal bacteria.