Abstract

Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation myelopoiesis is modulated to rapidly meet demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response in mice. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file.

Article and author information

Author details

  1. William David Jackson

    Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Chiara Giacomassi

    Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Sophie Ward

    Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Amber Owen

    National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Tiago C Luis

    Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6305-1257
  6. Sarah Spear

    Department of Surgery and Cancer, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4306-3752
  7. Kevin J Woollard

    Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9839-5463
  8. Cecilia Johansson

    National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Jessica Strid

    Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3690-2201
  10. Marina Botto

    Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
    For correspondence
    m.botto@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1458-3791

Funding

Wellcome Trust (108008/Z/15/Z)

  • Marina Botto

Wellcome Trust (102126/B/13/Z)

  • Cecilia Johansson

Wellcome Trust (Institutional Strategic Support Fund)

  • Chiara Giacomassi

Sir Henry Dale Fellowship -Wellcome Trust/Royal Society of Medicine (210424/Z/18/Z)

  • Tiago C Luis

Kay Kendall Leukaemia Fund (KKL1379)

  • Tiago C Luis

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

Reviewing Editor

  1. Paul W Noble, Cedars-Sinai Medical Center, United States

Ethics

Animal experimentation: All procedures were carried out in accordance with the institutional guidelines and the studies were approved by the UK Home Office. Experimental studies were designed according the ARRIVE guidelines.

Version history

  1. Received: December 17, 2022
  2. Preprint posted: February 7, 2023 (view preprint)
  3. Accepted: August 10, 2023
  4. Accepted Manuscript published: August 11, 2023 (version 1)
  5. Version of Record published: August 29, 2023 (version 2)

Copyright

© 2023, Jackson 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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  1. William David Jackson
  2. Chiara Giacomassi
  3. Sophie Ward
  4. Amber Owen
  5. Tiago C Luis
  6. Sarah Spear
  7. Kevin J Woollard
  8. Cecilia Johansson
  9. Jessica Strid
  10. Marina Botto
(2023)
TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity
eLife 12:e85647.
https://doi.org/10.7554/eLife.85647

Share this article

https://doi.org/10.7554/eLife.85647

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