Toxin-Triggered Interleukin-1 Receptor Signaling Enables Early-Life Discrimination of Pathogenic versus Commensal Skin Bacteria.

ABSTRACT: The host must develop tolerance to commensal microbes and protective responses to infectious pathogens, yet the mechanisms enabling a privileged relationship with commensals remain largely unknown. Skin colonization by commensal Staphylococcus epidermidis facilitates immune tolerance preferentially in neonates via induction of antigen-specific regulatory T cells (Tregs). Here, we demonstrate that this tolerance is not indiscriminately extended to all bacteria encountered in this early window. Rather, neonatal colonization by Staphylococcus aureus minimally enriches for antigen-specific Tregs and does not prevent skin inflammation upon later-life exposure. S. aureus ?-toxin contributes to this response by stimulating myeloid cell production of IL-1?, which limits S. aureus-specific Tregs. Loss of ?-toxin or the IL-1 receptor increases Treg enrichment, whereas topical application of IL-1? or ?-toxin diminishes tolerogenic responses to S. epidermidis. Thus, the preferential activation of a key alarmin pathway facilitates early discrimination of microbial "foe" from "friend," thereby preventing tolerance to a common skin pathogen.

SUBMITTER: Leech JM 

PROVIDER: S-EPMC6989301 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature