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TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung antiviral immunity
File(s)
elife-85647-v2.pdf (5.09 MB)
Published version
Author(s)
Jackson, William D
Giacomassi, Chiara
Ward, Sophie
Owen, Amber
Luis, Tiago C
Type
Journal Article
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 the 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.
Date Issued
2023-08-29
Date Acceptance
2023-08-10
Citation
eLife, 2023, 12
URI
URL
DOI
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Journal / Book Title
eLife
Volume
12
Copyright Statement
© Copyright Jackson,
Giacomassi et al. This article
is distributed under the terms
of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37566453
PII: 85647
Subjects
Animals
Cytokines
Lung
Mice
Mice, Inbred C57BL
Monocytes
Myelopoiesis
Toll-Like Receptor 7
Virus Diseases
haematopoiesis
immunology
inflammation
macrophages
monocytes
skin
TLR
virus
viruses
Publication Status
Published
Coverage Spatial
England
Article Number
e85647
Date Publish Online
2023-08-11