TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity
- Imperial College London, United Kingdom
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
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.
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.
Reviewing Editor
- Paul W Noble, Cedars-Sinai Medical Center, United States
Version history
- Received: December 17, 2022
- Preprint posted: February 7, 2023 (view preprint)
- Accepted: August 10, 2023
- Accepted Manuscript published: August 11, 2023 (version 1)
- 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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TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity
eLife 12:e85647.
https://doi.org/10.7554/eLife.85647
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