Contextual control of skin immunity and inflammation by Corynebacterium

Author:

Ridaura Vanessa K.1ORCID,Bouladoux Nicolas12ORCID,Claesen Jan3ORCID,Chen Y. Erin3,Byrd Allyson L.145,Constantinides Michael G.1ORCID,Merrill Eric D.1,Tamoutounour Samira1,Fischbach Michael A.3,Belkaid Yasmine12ORCID

Affiliation:

1. Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

2. Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

3. Department of Bioengineering, Stanford University, Stanford, CA

4. Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD

5. Department of Bioinformatics, Boston University, Boston, MA

Abstract

How defined microbes influence the skin immune system remains poorly understood. Here we demonstrate that Corynebacteria, dominant members of the skin microbiota, promote a dramatic increase in the number and activation of a defined subset of γδ T cells. This effect is long-lasting, occurs independently of other microbes, and is, in part, mediated by interleukin (IL)-23. Under steady-state conditions, the impact of Corynebacterium is discrete and noninflammatory. However, when applied to the skin of a host fed a high-fat diet, Corynebacterium accolens alone promotes inflammation in an IL-23–dependent manner. Such effect is highly conserved among species of Corynebacterium and dependent on the expression of a dominant component of the cell envelope, mycolic acid. Our data uncover a mode of communication between the immune system and a dominant genus of the skin microbiota and reveal that the functional impact of canonical skin microbial determinants is contextually controlled by the inflammatory and metabolic state of the host.

Funder

NIAID

Howard Hughes Medical Institute

Burroughs Wellcome Fund

National Institutes of H

ealth

Cancer Research Institute

European Molecular Biology Organization

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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