Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Research Article

MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype

Emilie Plantamura, Amiran Dzutsev, Mathias Chamaillard, View ORCID ProfileSophia Djebali, Lyvia Moudombi, Lilia Boucinha, Morgan Grau, Claire Macari, David Bauché, Oana Dumitrescu, Jean-Philippe Rasigade, Saskia Lippens, Michelina Plateroti, Elsa Kress, Annabelle Cesaro, Clovis Bondu, Ulrike Rothermel, Mathias Heikenwälder, Gerard Lina, Azzak Bentaher-Belaaouaj, Julien C. Marie, Christophe Caux, Giorgio Trinchieri, Jacqueline Marvel, and Marie-Cecile Michallet
  1. aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  2. bCancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702;
  3. cLeidos Biomedical Research, Inc., Frederick, MD 21702;
  4. dCenter for Infection and Immunity of Lille, Institut Pasteur de Lille, INSERM U1019, F-59000 Lille, France;
  5. eCenter for Infection and Immunity of Lille, University of Lille, F-59000 Lille, France;
  6. fUMR 8204, Centre National de la Recherche Scientifique, F-59000 Lille, France;
  7. gU1019, Team 7, Equipe Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale, F-59000 Lille, France;
  8. hCentre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, INSERM 1052, CNRS 5286, 69008 Lyon, France;
  9. iUniversity of Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France;
  10. jTransforming Growth Factor-b and Immune-Evasion Group, German Cancer Research Center, 69120 Heidelberg, Germany;
  11. kDepartment of Clinical Microbiology, Hospices Civils de Lyon, 69002 Lyon, France;
  12. lInflammation Research Center, Department of Biomedical Molecular Biology, Ghent University, Flanders Institute for Biotechnology, 9000 Ghent, Belgium;
  13. mChronic Inflammation and Cancer, German Cancer Research Center, 69120 Heidelberg, Germany

See allHide authors and affiliations

PNAS October 9, 2018 115 (41) 10404-10409; first published September 24, 2018; https://doi.org/10.1073/pnas.1722372115
Emilie Plantamura
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amiran Dzutsev
bCancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702;
cLeidos Biomedical Research, Inc., Frederick, MD 21702;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mathias Chamaillard
dCenter for Infection and Immunity of Lille, Institut Pasteur de Lille, INSERM U1019, F-59000 Lille, France;
eCenter for Infection and Immunity of Lille, University of Lille, F-59000 Lille, France;
fUMR 8204, Centre National de la Recherche Scientifique, F-59000 Lille, France;
gU1019, Team 7, Equipe Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale, F-59000 Lille, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sophia Djebali
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sophia Djebali
Lyvia Moudombi
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lilia Boucinha
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Morgan Grau
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Claire Macari
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Bauché
hCentre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, INSERM 1052, CNRS 5286, 69008 Lyon, France;
iUniversity of Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France;
jTransforming Growth Factor-b and Immune-Evasion Group, German Cancer Research Center, 69120 Heidelberg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oana Dumitrescu
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
kDepartment of Clinical Microbiology, Hospices Civils de Lyon, 69002 Lyon, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Philippe Rasigade
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
kDepartment of Clinical Microbiology, Hospices Civils de Lyon, 69002 Lyon, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saskia Lippens
lInflammation Research Center, Department of Biomedical Molecular Biology, Ghent University, Flanders Institute for Biotechnology, 9000 Ghent, Belgium;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michelina Plateroti
hCentre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, INSERM 1052, CNRS 5286, 69008 Lyon, France;
iUniversity of Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elsa Kress
hCentre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, INSERM 1052, CNRS 5286, 69008 Lyon, France;
iUniversity of Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annabelle Cesaro
dCenter for Infection and Immunity of Lille, Institut Pasteur de Lille, INSERM U1019, F-59000 Lille, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clovis Bondu
dCenter for Infection and Immunity of Lille, Institut Pasteur de Lille, INSERM U1019, F-59000 Lille, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ulrike Rothermel
mChronic Inflammation and Cancer, German Cancer Research Center, 69120 Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mathias Heikenwälder
mChronic Inflammation and Cancer, German Cancer Research Center, 69120 Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerard Lina
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
kDepartment of Clinical Microbiology, Hospices Civils de Lyon, 69002 Lyon, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Azzak Bentaher-Belaaouaj
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julien C. Marie
hCentre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, INSERM 1052, CNRS 5286, 69008 Lyon, France;
iUniversity of Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France;
jTransforming Growth Factor-b and Immune-Evasion Group, German Cancer Research Center, 69120 Heidelberg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christophe Caux
hCentre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, INSERM 1052, CNRS 5286, 69008 Lyon, France;
iUniversity of Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giorgio Trinchieri
bCancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacqueline Marvel
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie-Cecile Michallet
aCentre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: marie-cecile.michallet@lyon.unicancer.fr
  1. Edited by Lora V. Hooper, University of Texas Southwestern Medical Center, Dallas, TX, and approved August 16, 2018 (received for review January 4, 2018)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Growing evidence suggests that prominent changes in the gut microbial communities (dysbiosis) play a key role in the development of allergic disorders, but the underlying mechanisms remain largely unknown. Here, we used a murine model of human allergic contact dermatitis to demonstrate a regulatory role of the adaptor mitochondrial antiviral signaling (MAVS) RIG-I–like receptors on disease outcome by modulating gut barrier function and bacterial ecology. Our results highlight an unexpected role of the RIG-I–MAVS pathway in maintenance of intestinal barrier function and modulation of gut commensal flora to prevent the development of inflammatory diseases such as allergy. These data provide a rationale for manipulating the gut microbiota as a therapeutic intervention in subjects at risk of developing allergy.

Abstract

Prominent changes in the gut microbiota (referred to as “dysbiosis”) play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I–like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs−/− mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I–like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.

  • RIG-like receptors
  • MAVS
  • dysbiosis
  • allergic skin pathologies

Footnotes

  • ↵1Present address: MaaT Pharma, 69007 Lyon, France.

  • ↵2A.D. and M.C. contributed equally to this work.

  • ↵3Present address: Department of Immunity, Virus and Infammation (IVI), Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, 69008 Lyon, France.

  • ↵4To whom correspondence should be addressed. Email: marie-cecile.michallet{at}lyon.unicancer.fr.
  • Author contributions: E.P., S.D., O.D., M.P., G.L., J.M., and M.-C.M. designed research; E.P., A.D., S.D., L.M., L.B., M.G., C.M., D.B., J.-P.R., S.L., M.P., E.K., A.C., C.B., U.R., M.H., and M.-C.M. performed research; E.P., S.D., O.D., M.P., G.L., J.M., and M.-C.M. analyzed data; and E.P., A.D., M.C., A.B.-B., J.C.M., C.C., G.T., J.M., and M.-C.M. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1722372115/-/DCSupplemental.

Published under the PNAS license.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype
Emilie Plantamura, Amiran Dzutsev, Mathias Chamaillard, Sophia Djebali, Lyvia Moudombi, Lilia Boucinha, Morgan Grau, Claire Macari, David Bauché, Oana Dumitrescu, Jean-Philippe Rasigade, Saskia Lippens, Michelina Plateroti, Elsa Kress, Annabelle Cesaro, Clovis Bondu, Ulrike Rothermel, Mathias Heikenwälder, Gerard Lina, Azzak Bentaher-Belaaouaj, Julien C. Marie, Christophe Caux, Giorgio Trinchieri, Jacqueline Marvel, Marie-Cecile Michallet
Proceedings of the National Academy of Sciences Oct 2018, 115 (41) 10404-10409; DOI: 10.1073/pnas.1722372115

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype
Emilie Plantamura, Amiran Dzutsev, Mathias Chamaillard, Sophia Djebali, Lyvia Moudombi, Lilia Boucinha, Morgan Grau, Claire Macari, David Bauché, Oana Dumitrescu, Jean-Philippe Rasigade, Saskia Lippens, Michelina Plateroti, Elsa Kress, Annabelle Cesaro, Clovis Bondu, Ulrike Rothermel, Mathias Heikenwälder, Gerard Lina, Azzak Bentaher-Belaaouaj, Julien C. Marie, Christophe Caux, Giorgio Trinchieri, Jacqueline Marvel, Marie-Cecile Michallet
Proceedings of the National Academy of Sciences Oct 2018, 115 (41) 10404-10409; DOI: 10.1073/pnas.1722372115
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

Article Classifications

  • Biological Sciences
  • Immunology and Inflammation
Proceedings of the National Academy of Sciences: 115 (41)
Table of Contents

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion/Conclusion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Water from a faucet fills a glass.
News Feature: How “forever chemicals” might impair the immune system
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Reflection of clouds in the still waters of Mono Lake in California.
Inner Workings: Making headway with the mysteries of life’s origins
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Cave in coastal Kenya with tree growing in the middle.
Journal Club: Small, sharp blades mark shift from Middle to Later Stone Age in coastal Kenya
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Mouse fibroblast cells. Electron bifurcation reactions keep mammalian cells alive.
Exploring electron bifurcation
Jonathon Yuly, David Beratan, and Peng Zhang investigate how electron bifurcation reactions work.
Listen
Past PodcastsSubscribe
Panda bear hanging in a tree
How horse manure helps giant pandas tolerate cold
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Cozzarelli Prize
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490