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CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis

Macrophages facilitate critical functions in regulating pathogen clearance and immune homeostasis in tissues. The remarkable functional diversity exhibited by macrophage subsets is dependent on tissue environment and the nature of the pathological insult. Our current knowledge of the mechanisms that...

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Autores principales: Yeung, Stephen T., Ovando, Luis J., Russo, Ashley J., Rathinam, Vijay A., Khanna, Kamal M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123955/
https://www.ncbi.nlm.nih.gov/pubmed/36867536
http://dx.doi.org/10.1016/j.celrep.2023.112171
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author Yeung, Stephen T.
Ovando, Luis J.
Russo, Ashley J.
Rathinam, Vijay A.
Khanna, Kamal M.
author_facet Yeung, Stephen T.
Ovando, Luis J.
Russo, Ashley J.
Rathinam, Vijay A.
Khanna, Kamal M.
author_sort Yeung, Stephen T.
collection PubMed
description Macrophages facilitate critical functions in regulating pathogen clearance and immune homeostasis in tissues. The remarkable functional diversity exhibited by macrophage subsets is dependent on tissue environment and the nature of the pathological insult. Our current knowledge of the mechanisms that regulate the multifaceted counter-inflammatory responses mediated by macrophages remains incomplete. Here, we report that CD169+ macrophage subsets are necessary for protection under excessive inflammatory conditions. We show that in the absence of these macrophages, even under mild septic conditions, mice fail to survive and exhibit increased production of inflammatory cytokines. Mechanistically, CD169+ macrophages control inflammatory responses via interleukin-10 (IL-10), as CD169+ macrophage-specific deletion of IL-10 was lethal during septic conditions, and recombinant IL-10 treatment reduced lipopolysaccharide (LPS)-induced lethality in mice lacking CD169+ macrophages. Collectively, our findings show a pivotal homeostatic role for CD169+ macrophages and suggest they may serve as an important target for therapy under damaging inflammatory conditions.
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spelling pubmed-101239552023-04-24 CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis Yeung, Stephen T. Ovando, Luis J. Russo, Ashley J. Rathinam, Vijay A. Khanna, Kamal M. Cell Rep Article Macrophages facilitate critical functions in regulating pathogen clearance and immune homeostasis in tissues. The remarkable functional diversity exhibited by macrophage subsets is dependent on tissue environment and the nature of the pathological insult. Our current knowledge of the mechanisms that regulate the multifaceted counter-inflammatory responses mediated by macrophages remains incomplete. Here, we report that CD169+ macrophage subsets are necessary for protection under excessive inflammatory conditions. We show that in the absence of these macrophages, even under mild septic conditions, mice fail to survive and exhibit increased production of inflammatory cytokines. Mechanistically, CD169+ macrophages control inflammatory responses via interleukin-10 (IL-10), as CD169+ macrophage-specific deletion of IL-10 was lethal during septic conditions, and recombinant IL-10 treatment reduced lipopolysaccharide (LPS)-induced lethality in mice lacking CD169+ macrophages. Collectively, our findings show a pivotal homeostatic role for CD169+ macrophages and suggest they may serve as an important target for therapy under damaging inflammatory conditions. 2023-03-28 2023-03-02 /pmc/articles/PMC10123955/ /pubmed/36867536 http://dx.doi.org/10.1016/j.celrep.2023.112171 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Yeung, Stephen T.
Ovando, Luis J.
Russo, Ashley J.
Rathinam, Vijay A.
Khanna, Kamal M.
CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis
title CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis
title_full CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis
title_fullStr CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis
title_full_unstemmed CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis
title_short CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis
title_sort cd169+ macrophage intrinsic il-10 production regulates immune homeostasis during sepsis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123955/
https://www.ncbi.nlm.nih.gov/pubmed/36867536
http://dx.doi.org/10.1016/j.celrep.2023.112171
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