Article | Published:

A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes

Nature Immunology volume 18, pages 13101320 (2017) | Download Citation

  • A Correction to this article was published on 28 June 2018

Abstract

The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions. Monocyte-derived AMs blocked the ability of dendritic cells to trigger a HDM-specific response by the TH2 subset of helper T cells. Our results indicate that replacement of embryonic AMs by regulatory monocytes is a major mechanism underlying the long-term training of lung immunity after infection.

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Acknowledgements

We thank U. Eriksson (Center for Molecular Cardiology, University of Zurich) for BALB/c CD45.1+ genitor mice; A. Osterhaus, T. Marichal and C. Desmet for critical discussions; and L. Dams, C. Delforge, E. Deglaire, C. Espert, A. Guillaume, M. Sarlet and A. Vanderlinden for technical and secretary assistance. Supported by the University of Liège (VIR-IMPRINT ARC), “Fonds de la Recherche Scientifique - Fonds National Belge de la Recherche Scientifique” (“credit de recherche” J007515F; “projet de recherche” T.0195.16; research associate support for B.D.) and Institut MERIEUX (starting grant).

Author information

Author notes

    • Bénédicte Machiels
    •  & Mickael Dourcy

    These authors contributed equally to this work.

Affiliations

  1. Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine – FARAH, University of Liège, Liège, Belgium.

    • Bénédicte Machiels
    • , Mickael Dourcy
    • , Xue Xiao
    • , Justine Javaux
    • , Benjamin Dewals
    • , Alain Vanderplasschen
    •  & Laurent Gillet
  2. Cellular and Molecular Immunology, Department of Functional Sciences, Faculty of Veterinary Medicine – GIGA, University of Liège, Liège, Belgium.

    • Claire Mesnil
    • , Catherine Sabatel
    •  & Fabrice Bureau
  3. Department of Pathology, Faculty of Veterinary Medicine – FARAH, University of Liège, Liège, Belgium.

    • Daniel Desmecht
  4. Department of Radiology, University Hospital Liège, Liège, Belgium.

    • François Lallemand
    •  & Philippe Martinive
  5. VIB Center for Inflammation Research, Ghent University, Ghent, Belgium.

    • Hamida Hammad
    • , Martin Guilliams
    •  & Bart N Lambrecht
  6. Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Bart N Lambrecht

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Contributions

B.M., M.D. and L.G. designed the experiments with the help of H.H., M.G., B.N.L. and F.B.; B.M. and M.D. did most of the experiments and compiled the data; B.M., M.D., X.X. and L.G. prepared the figures; X.X. performed the transcriptomic and statistical analyses; J.J., C.M., C.S., F.L., and P.M. were involved in specific experiments; B.M., M.D., D.D., H.H., M.G., B.D., A.V., B.N.L., F.B. and L.G. analyzed the data; and B.M., M.D. and L.G. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Laurent Gillet.

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DOI

https://doi.org/10.1038/ni.3857

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