Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes

Summary: Alveolar macrophages (AMs) are lung-resident macrophages critical to lung homeostasis and immunity. Replacement of embryonic-derived tissue-resident AMs (TRAMs) by circulating monocyte-derived AMs (MoAMs) reshapes the functionality of AMs and host susceptibility to respiratory diseases. How...

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Main Authors: Jinjing Zhang, Tao Wang, Yanling Wang, Ying Li, Lu Wang, Jiepu Wang, Yuxuan Miao, Feng Xu, Yushi Yao
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725003420
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author Jinjing Zhang
Tao Wang
Yanling Wang
Ying Li
Lu Wang
Jiepu Wang
Yuxuan Miao
Feng Xu
Yushi Yao
author_facet Jinjing Zhang
Tao Wang
Yanling Wang
Ying Li
Lu Wang
Jiepu Wang
Yuxuan Miao
Feng Xu
Yushi Yao
author_sort Jinjing Zhang
collection DOAJ
description Summary: Alveolar macrophages (AMs) are lung-resident macrophages critical to lung homeostasis and immunity. Replacement of embryonic-derived tissue-resident AMs (TRAMs) by circulating monocyte-derived AMs (MoAMs) reshapes the functionality of AMs and host susceptibility to respiratory diseases. However, mechanisms underlying such an AM turnover remain unclear. Using a mouse model of Streptococcus pneumoniae (S.P.) infection, we show here that respiratory S.P. infection induces the recruitment and differentiation of MoAMs, which dominate the post-infectious AM population and are functionally hyperresponsive. This turnover of AMs is not due to S.P.-induced irreversible loss of TRAMs. Instead, TRAMs experience a quick recovery in cell number shortly after the resolution of S.P. infection. While S.P.-experienced TRAMs keep the potential of long-term self-maintenance in a non-competitive environment, they demonstrate cellular senescence and a reduced rate of homeostatic proliferation and are, therefore, outcompeted by MoAMs. These data provide new insights into the mechanisms and functional significance of AM turnover during pulmonary bacterial infection.
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publishDate 2025-05-01
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series Cell Reports
spelling doaj-art-cc50eeb4dad3466bb92d9a67fc1c7c6e2025-08-20T02:17:26ZengElsevierCell Reports2211-12472025-05-0144511557110.1016/j.celrep.2025.115571Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytesJinjing Zhang0Tao Wang1Yanling Wang2Ying Li3Lu Wang4Jiepu Wang5Yuxuan Miao6Feng Xu7Yushi Yao8Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, ChinaInstitute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, Hangzhou 310023, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China; Corresponding authorSummary: Alveolar macrophages (AMs) are lung-resident macrophages critical to lung homeostasis and immunity. Replacement of embryonic-derived tissue-resident AMs (TRAMs) by circulating monocyte-derived AMs (MoAMs) reshapes the functionality of AMs and host susceptibility to respiratory diseases. However, mechanisms underlying such an AM turnover remain unclear. Using a mouse model of Streptococcus pneumoniae (S.P.) infection, we show here that respiratory S.P. infection induces the recruitment and differentiation of MoAMs, which dominate the post-infectious AM population and are functionally hyperresponsive. This turnover of AMs is not due to S.P.-induced irreversible loss of TRAMs. Instead, TRAMs experience a quick recovery in cell number shortly after the resolution of S.P. infection. While S.P.-experienced TRAMs keep the potential of long-term self-maintenance in a non-competitive environment, they demonstrate cellular senescence and a reduced rate of homeostatic proliferation and are, therefore, outcompeted by MoAMs. These data provide new insights into the mechanisms and functional significance of AM turnover during pulmonary bacterial infection.http://www.sciencedirect.com/science/article/pii/S2211124725003420CP: Immunology
spellingShingle Jinjing Zhang
Tao Wang
Yanling Wang
Ying Li
Lu Wang
Jiepu Wang
Yuxuan Miao
Feng Xu
Yushi Yao
Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes
Cell Reports
CP: Immunology
title Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes
title_full Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes
title_fullStr Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes
title_full_unstemmed Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes
title_short Bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes
title_sort bacterial pneumonia induces senescence in resident alveolar macrophages that are outcompeted by monocytes
topic CP: Immunology
url http://www.sciencedirect.com/science/article/pii/S2211124725003420
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