1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through STING

  1. Sytse J Piersma  Is a corresponding author
  2. Jennifer Poursine-Laurent
  3. Liping Yang
  4. Glen Barber
  5. Bijal A Parikh
  6. Wayne M Yokoyama
  1. Washington University School of Medicine, United States
  2. University of Miami Miller School of Medicine, United States
Research Article
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Cite this article as: eLife 2020;9:e56882 doi: 10.7554/eLife.56882

Abstract

Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while we confirmed plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.

Article and author information

Author details

  1. Sytse J Piersma

    Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St Louis, United States
    For correspondence
    spiersma@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5379-3556
  2. Jennifer Poursine-Laurent

    Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Liping Yang

    Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Glen Barber

    University of Miami Miller School of Medicine, Miami, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Bijal A Parikh

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Wayne M Yokoyama

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0566-7264

Funding

National Institute of Allergy and Infectious Diseases (R01-AI131680)

  • Wayne M Yokoyama

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Rubicon grant 825.11.004)

  • Sytse J Piersma

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to the approved institutional animal care and use committee (IACUC) protocol (#20180293). The protocol was approved by the Animal Studies Committee of Washington University.

Reviewing Editor

  1. Stipan Jonjic, University Rijeka, Croatia

Publication history

  1. Received: March 12, 2020
  2. Accepted: July 27, 2020
  3. Accepted Manuscript published: July 29, 2020 (version 1)
  4. Version of Record published: August 7, 2020 (version 2)

Copyright

© 2020, Piersma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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