Editors' ChoiceHost-Microbe Interactions

Distinguishing friend from foe

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Science Signaling  17 Dec 2019:
Vol. 12, Issue 612, eaba5393
DOI: 10.1126/scisignal.aba5393

Toxin-stimulated immune signaling helps neonatal mice distinguish between harmless skin colonizers and potential pathogens.

Interactions between commensal bacteria and tissue-resident immune cells promote both tolerance to commensals and immunity to pathogens. Tolerance depends on the development of T regulatory cells (Tregs) that suppress immune responses to commensals. This is particularly important during the neonatal period when tissues are initially colonized, and the organism must be able to discriminate between harmless species and pathogenic ones (see commentary by Xing and Naik). Leech et al. found that neonatal mice colonized with a strain of the commensal skin bacterium Staphylococcus epidermidis expressing a synthetic peptide antigen produced a high number of antigen-specific Tregs and were protected from inflammation when challenged by cutaneous infection with S. epidermidis as adults. Those colonized with a strain of the pathobiont (potential pathogen) Staphylococcus aureus expressing the same synthetic peptide antigen had fewer antigen-specific Tregs and exhibited inflammation when challenged with S. aureus as adults. Transcriptomic analysis implicated interleukin-1β (IL-1β) signaling in the differential stimulation of Tregs by the two species, and bone marrow–derived myeloid cells stimulated with S. aureus secreted more IL-1β than did cells stimulated with S. epidermidis. Colonization with S. aureus increased the number of antigen-specific Tregs in IL-1R knockout mice compared with wild-type mice, but IL-1R knockout had no effect on the number of antigen-specific Tregs in mice colonized S. epidermidis. An S. aureus strain that does not produce α-toxin, which stimulates the secretion of IL-1β, stimulated more Tregs than did the wild-type strain, and application of purified α-toxin to the skin of S. epidermidis–colonized neonates reduced the production of antigen-specific Tregs. Thus, immune signaling elicited by a toxin can enable neonates to distinguish between harmless and potentially harmful bacteria.

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