Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota

Djalma S. Lima-Junior; Siddharth R. Krishnamurthy; Nicolas Bouladoux; Nicholas Collins; Seong-Ji Han; Erin Y. Chen; Michael G. Constantinides; Verena M. Link; Ai Ing Lim; Michel Enamorado; Christophe Cataisson; Louis Gil; Indira Rao; Taylor K. Farley; Galina Koroleva; Jan Attig; Stuart H. Yuspa; Michael A. Fischbach; George Kassiotis; Yasmine Belkaid

doi:10.1016/j.cell.2021.05.020

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Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota

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Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota

Djalma S. Lima-Junior, Siddharth R. Krishnamurthy, Nicolas Bouladoux, Nicholas Collins, Seong-Ji Han, Erin Y. Chen, Michael G. Constantinides, Verena M. Link, Ai Ing Lim, Michel Enamorado, …

Cell, Vol.184(14), pp.3794-3811.e19

08/07/2021

DOI: https://doi.org/10.1016/j.cell.2021.05.020

PMID: 34166614

Résumé

antiretroviral

endogenous retrovirus

high fat diet

keratinocytes

microbiota

skin immunity

Staphylococcus epidermidis

STING

T cells

tissue repair

The microbiota plays a fundamental role in regulating host immunity. However, the processes involved in the initiation and regulation of immunity to the microbiota remain largely unknown. Here, we show that the skin microbiota promotes the discrete expression of defined endogenous retroviruses (ERVs). Keratinocyte-intrinsic responses to ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes protein (STING) signaling and promoted the induction of commensal-specific T cells. Inhibition of ERV reverse transcription significantly impacted these responses, resulting in impaired immunity to the microbiota and its associated tissue repair function. Conversely, a lipid-enriched diet primed the skin for heightened ERV- expression in response to commensal colonization, leading to increased immune responses and tissue inflammation. Together, our results support the idea that the host may have co-opted its endogenous virome as a means to communicate with the exogenous microbiota, resulting in a multi-kingdom dialog that controls both tissue homeostasis and inflammation. [Display omitted] •Endogenous retrovirus sensing is required for commensal-specific immunity•Reverse transcription inhibition impairs commensal-induced immunity in the skin•cGAS/STING signaling in keratinocytes is required for skin immunity to the microbiota•Enhanced endogenous retrovirus expression promotes microbiota-induced inflammation The host immune system uses the endogenous virome to communicate with the exogenous microbiota in a multi-kingdom interaction that modulates tissue repair or inflammation.

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Détails

Titre: Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota
Créateurs - sans rôle: Djalma S. Lima-Junior - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Siddharth R. Krishnamurthy - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Nicolas Bouladoux - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Nicholas Collins - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Seong-Ji Han - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Erin Y. Chen - Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA
Michael G. Constantinides - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Verena M. Link - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Ai Ing Lim - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Michel Enamorado - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Christophe Cataisson - In Vitro Pathogenesis Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Louis Gil - NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Indira Rao - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Taylor K. Farley - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Galina Koroleva - NIH Center for Human Immunology, Bethesda, MD 20896, USA
Jan Attig - Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Stuart H. Yuspa - In Vitro Pathogenesis Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Michael A. Fischbach - Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA
George Kassiotis - Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Yasmine Belkaid - Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Détails de publication: Cell, Vol.184(14), pp.3794-3811.e19
Éditeur: Elsevier Inc
Identifiants: 99155841609311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article