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

Autor:	Leech JM; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Dhariwala MO; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Lowe MM; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Chu K; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Merana GR; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Cornuot C; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Weckel A; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Ma JM; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Leitner EG; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Gonzalez JR; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Vasquez KS; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Diep BA; Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Scharschmidt TC; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: tiffany.scharschmidt@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2019 Dec 11; Vol. 26 (6), pp. 795-809.e5. Date of Electronic Publication: 2019 Nov 26.
DOI:	10.1016/j.chom.2019.10.007
Abstrakt:	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 α-toxin contributes to this response by stimulating myeloid cell production of IL-1β, which limits S. aureus-specific Tregs. Loss of α-toxin or the IL-1 receptor increases Treg enrichment, whereas topical application of IL-1β or α-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. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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