Competition between skin antimicrobial peptides and commensal bacteria in type 2 inflammation enables survival of S. aureus

Teruaki Nakatsuji; Samantha L. Brinton; Kellen J. Cavagnero; Alan M. O’Neill; Yang Chen; Tatsuya Dokoshi; Anna M. Butcher; Olive C. Osuoji; Faiza Shafiq; Josh L. Espinoza; Christopher L. Dupont; Tissa R. Hata; Richard L. Gallo

Cell Reports (May 2023)

Competition between skin antimicrobial peptides and commensal bacteria in type 2 inflammation enables survival of S. aureus

Teruaki Nakatsuji,
Samantha L. Brinton,
Kellen J. Cavagnero,
Alan M. O’Neill,
Yang Chen,
Tatsuya Dokoshi,
Anna M. Butcher,
Olive C. Osuoji,
Faiza Shafiq,
Josh L. Espinoza,
Christopher L. Dupont,
Tissa R. Hata,
Richard L. Gallo

Affiliations

Teruaki Nakatsuji: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Samantha L. Brinton: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Kellen J. Cavagnero: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Alan M. O’Neill: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Yang Chen: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Tatsuya Dokoshi: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Anna M. Butcher: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Olive C. Osuoji: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Faiza Shafiq: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Josh L. Espinoza: Genomic Medicine, J. Craig Venter Institute, La Jolla, CA 92037, USA
Christopher L. Dupont: Genomic Medicine, J. Craig Venter Institute, La Jolla, CA 92037, USA
Tissa R. Hata: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA
Richard L. Gallo: Department of Dermatology, University of California, San Diego, La Jolla, CA 92037, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 5
p. 112494

Abstract

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Summary: During inflammation, the skin deploys antimicrobial peptides (AMPs) yet during allergic inflammation it becomes more susceptible to Staphylococcus aureus. To understand this contradiction, single-cell sequencing of Il4ra−/− mice combined with skin microbiome analysis reveals that lower production of AMPs from interleukin-4 receptor α (IL-4Rα) activation selectively inhibits survival of antibiotic-producing strains of coagulase-negative Staphylococcus (CoNS). Diminished AMPs under conditions of T helper type 2 (Th2) inflammation enable expansion of CoNS strains without antibiotic activity and increase Staphylococcus aureus (S. aureus), recapitulating the microbiome on humans with atopic dermatitis. This response is rescued in Camp−/− mice or after topical steroids, since further inhibition of AMPs enables survival of antibiotic-producing CoNS strains. In conditions of Th17 inflammation, a higher expression of host AMPs is sufficient to directly inhibit S. aureus survival. These results show that antimicrobials produced by the host and commensal bacteria each act to control S. aureus on the skin.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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