ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Infectious Agents and Disease
This article is part of the Research TopicInflammation's Dual Role in Viral Respiratory InfectionsView all articles
Skewed pulmonary innate immune cell composition underlies the delayed influenza clearance in aged mice
Provisionally accepted
- 1Department of Infectious Diseases, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital,Fudan University, Shanghai, China
- 2Department of laboratory medicine, Shanghai Public Health Clinical Center, Shanghai, China
- 3Department of Radiology, Shanghai Public Health Clinical Center, Shanghai, China
- 4Department of Imaging and Interventional Radiology, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China
- 5Shanghai Sci-Tech InnoCenter for Infection and Immunity, Shanghai, China
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Aging increases vulnerability of the elderly to influenza, but the mechanisms have not been fully understood. Lethally infected aged mice are frequently used as models of influenza infection in the elderly. It is a relevant model for investigating mechanisms underlying the higher mortality in influenza-infected elderly, but might not be the most appropriate model to study the increased disease severity. In this study, we characterized the viral replication, pulmonary innate immune cell composition and the transcription levels of a panel of cytokines in adult (8–12 months) and aged (22– 24 months) mice after sublethal H1N1 (PR8) infection. Despite similar body weight loss, the aged mice showed significantly higher lung viral titers at day 8. Notably, key innate immune populations, including alveolar macrophages, neutrophils, and eosinophils, showed distinct age-related patterns. In the adult mice, alveolar macrophages negatively correlated with weight loss, whereas no protective immune factor was identified in the aged mice. Moreover, our data showed that persistent viral replication led to distinct innate immune cell composition in the adult and aged mice despite comparable transcription levels of inflammatory cytokines. The numbers and frequencies of both the neutrophils and eosinophils were significantly higher in the virus-persistent adult mice than those in the virus-persistent aged mice. Our findings highlight the skewed acute responses against influenza infection in the lungs of aged mice, which might partly explain their mild weight loss despite delayed viral clearance upon influenza infection.
Keywords: aging1, influenza2, sublethal infection3, innate immune cel4, inflammatory cytokine5
Received: 28 Oct 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Cheng, Zhao, Wu, Wan, Zhu and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhaoqin Zhu
Jialin Jin
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