ArticleCell2021
Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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127 citing papers in PubMed, 187 citations in OpenAlex.
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- Locus-specific HERV expression identifies an aggressive, NK-depleted, checkpoint-refractory acral melanoma phenotype.Frontiers in medicine · 2026Article
- Analysis of the profiles of human endogenous retroviruses W, K, and H and the systemic inflammatory status in vitiligo patients: insights on the dynamics of endogenous retroviral expression and its interplay with inflammatory response.Frontiers in cellular and infection microbiology · 2026Article
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- Estrogen-Driven Breast Carcinogenesis in a Rat Model is Linked to Retroelement Activation and Inflammation and is Susceptible to Lamivudine Treatment.Breast cancer (Dove Medical Press) · 2026Article
- Oncogenic role of ERV with therapeutic potential.Frontiers in immunology · 2026Review
- Maladaptive immunity to the microbiota promotes neuronal hyperinnervation and itch via IL-17A.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 8 institutions in 2 countries.
Djalma S Lima-JuniorMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Siddharth R KrishnamurthyMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nicolas BouladouxMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nicholas CollinsMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Seong-Ji HanMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Erin Y ChenDepartment of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
Michael G ConstantinidesMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Verena M LinkMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIH Center for Human Immunology, Bethesda, MD 20896, USA.
Ai Ing LimMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Michel EnamoradoMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Christophe CataissonIn 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 GilNIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Indira RaoMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Taylor K FarleyMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UK.
Galina KorolevaNIH Center for Human Immunology, Bethesda, MD 20896, USA.
Jan AttigRetroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK.
Stuart H YuspaIn 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 FischbachDepartment of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
George KassiotisRetroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK.
Yasmine BelkaidMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: ybelkaid@niaid.nih.gov.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USStanford University · USCenter for Cancer Research · USImperial College London · GBNational Cancer Institute · USThe Francis Crick Institute · GBUniversity of Oxford · GB
Funding
Role of the microbiota in immunityZIAAI001115 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2009 to 2025
$22.4MNIAID Microbiome ProgramZICAI001233 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOUTSOPOULOS, NIKI · 2018 to 2025
$18.9MInteracting Signaling Pathways that Initiate Squamous Cell CarcinogenesisZIABC004504 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI YUSPA, STUART H. · 2009 to 2022
$15.7MPathways that Suppress or Accelerate Premalignant Progression of Squamous CancerZIABC005445 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI YUSPA, STUART H. · 2009 to 2022
$15.7MRole of Tissue-Specific Factors in the Control of ImmunityZIAAI001132 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2011 to 2025
$6.4MRole of Vitamins in the Control of ImmunityZIAAI001133 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2010 to 2025
$6.1MA complete map of the top 100 molecules from the gut microbiomeDP1DK113598 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FISCHBACH, MICHAEL ANDREW · 2016 to 2020
$5.5MIdentification and characterization of natural products from the human microbiotaR01DK110174 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FISCHBACH, MICHAEL ANDREW · 2016 to 2019
$1.4MCancer Research UKHoward Hughes Medical InstituteIntramural NIH HHS ZIA AI001115Intramural NIH HHS ZIA AI001132Medical Research CouncilNCI NIH HHS K99 CA252443NIDDK NIH HHS DP1 DK113598NIDDK NIH HHS R01 DK110174Wellcome Trust 102898/B/13/ZWellcome Trust FC001078Wellcome Trust FC001099
Abstract
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.
Indexed as
HomeostasisMicrobiotaAnimalsBacteriaChromosomes, BacterialCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDiet, High-FatEndogenous RetrovirusesInflammationInterferon Type IKeratinocytesMembrane ProteinsMiceMice, Inbred C57BLNucleotidyltransferasesRetroelementscGAS protein, mouseCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon Type IMembrane ProteinsNucleotidyltransferasesRetroelementsSting1 protein, mouseSTING Proteinantiretroviralendogenous retrovirushigh fat dietkeratinocytesmicrobiotaskin immunityStaphylococcus epidermidisSTINGT cellstissue repair
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