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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Summary: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.
ISSN:2211-1247