Cargando…

Neutrophil S100A9 supports M2 macrophage niche formation in granulomas

Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed...

Descripción completa

Detalles Bibliográficos
Autores principales: Mizutani, Tatsuaki, Ano, Toshiaki, Yoshioka, Yuya, Mizuta, Satoshi, Takemoto, Keiko, Ouchi, Yuki, Morita, Daisuke, Kitano, Satsuki, Miyachi, Hitoshi, Tsuruyama, Tatsuaki, Fujiwara, Nagatoshi, Sugita, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947307/
https://www.ncbi.nlm.nih.gov/pubmed/36843852
http://dx.doi.org/10.1016/j.isci.2023.106081
_version_ 1784892523993366528
author Mizutani, Tatsuaki
Ano, Toshiaki
Yoshioka, Yuya
Mizuta, Satoshi
Takemoto, Keiko
Ouchi, Yuki
Morita, Daisuke
Kitano, Satsuki
Miyachi, Hitoshi
Tsuruyama, Tatsuaki
Fujiwara, Nagatoshi
Sugita, Masahiko
author_facet Mizutani, Tatsuaki
Ano, Toshiaki
Yoshioka, Yuya
Mizuta, Satoshi
Takemoto, Keiko
Ouchi, Yuki
Morita, Daisuke
Kitano, Satsuki
Miyachi, Hitoshi
Tsuruyama, Tatsuaki
Fujiwara, Nagatoshi
Sugita, Masahiko
author_sort Mizutani, Tatsuaki
collection PubMed
description Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Because the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas.
format Online
Article
Text
id pubmed-9947307
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-99473072023-02-24 Neutrophil S100A9 supports M2 macrophage niche formation in granulomas Mizutani, Tatsuaki Ano, Toshiaki Yoshioka, Yuya Mizuta, Satoshi Takemoto, Keiko Ouchi, Yuki Morita, Daisuke Kitano, Satsuki Miyachi, Hitoshi Tsuruyama, Tatsuaki Fujiwara, Nagatoshi Sugita, Masahiko iScience Article Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Because the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas. Elsevier 2023-01-31 /pmc/articles/PMC9947307/ /pubmed/36843852 http://dx.doi.org/10.1016/j.isci.2023.106081 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mizutani, Tatsuaki
Ano, Toshiaki
Yoshioka, Yuya
Mizuta, Satoshi
Takemoto, Keiko
Ouchi, Yuki
Morita, Daisuke
Kitano, Satsuki
Miyachi, Hitoshi
Tsuruyama, Tatsuaki
Fujiwara, Nagatoshi
Sugita, Masahiko
Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
title Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
title_full Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
title_fullStr Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
title_full_unstemmed Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
title_short Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
title_sort neutrophil s100a9 supports m2 macrophage niche formation in granulomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947307/
https://www.ncbi.nlm.nih.gov/pubmed/36843852
http://dx.doi.org/10.1016/j.isci.2023.106081
work_keys_str_mv AT mizutanitatsuaki neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT anotoshiaki neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT yoshiokayuya neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT mizutasatoshi neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT takemotokeiko neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT ouchiyuki neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT moritadaisuke neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT kitanosatsuki neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT miyachihitoshi neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT tsuruyamatatsuaki neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT fujiwaranagatoshi neutrophils100a9supportsm2macrophagenicheformationingranulomas
AT sugitamasahiko neutrophils100a9supportsm2macrophagenicheformationingranulomas