Aging exacerbates damage and delays repair of alveolar epithelia following influenza viral pneumonia

Respiratory Research

Jianzhu Chen¹  Vincent TK Chow²  Hanry Yu³  Jagath C Rajapakse⁵  Shuoyu Xu⁵  Nicola HN Leung⁴  Gino V Limmon⁴  Dahai Zheng⁴  Lu Yin⁴ 

[1] The Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 76-261, Cambridge 02139, MA, USA;Host And Pathogen Interactivity Laboratory, Department of Microbiology, School of Medicine, National University Health System, National University of Singapore, Singapore, Singapore;Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore, Singapore;Bioinformatics Research Center, School of Computer Engineering, Nanyang Technological University of Singapore, Singapore, Singapore

关键词: Pro-SPC-positive bronchiolar epithelial cell;    Club cell;    Alveolar type II cell;    Alveolar type I cell;    Imaging analysis;    Lung damage repair;    Aged;    Influenza;   

Others  :  1137261
DOI  :  10.1186/s12931-014-0116-z

 received in 2014-06-09, accepted in 2014-09-15,  发布年份 2014

【 摘 要 】

Background

Influenza virus infection causes significantly higher levels of morbidity and mortality in the elderly. Studies have shown that impaired immunity in the elderly contributes to the increased susceptibility to influenza virus infection, however, how aging affects the lung tissue damage and repair has not been completely elucidated.

Methods

Aged (16–18 months old) and young (2–3 months old) mice were infected with influenza virus intratracheally. Body weight and mortality were monitored. Different days after infection, lung sections were stained to estimate the overall lung tissue damage and for club cells, pro-SPC⁺ bronchiolar epithelial cells, alveolar type I and II cells to quantify their frequencies using automated image analysis algorithms.

Results

Following influenza infection, aged mice lose more weight and die from otherwise sub-lethal influenza infection in young mice. Although there is no difference in damage and regeneration of club cells between the young and the aged mice, damage to alveolar type I and II cells (AT1s and AT2s) is exacerbated, and regeneration of AT2s and their precursors (pro-SPC-positive bronchiolar epithelial cells) is significantly delayed in the aged mice. We further show that oseltamivir treatment reduces virus load and lung damage, and promotes pulmonary recovery from infection in the aged mice.

Conclusions

These findings show that aging increases susceptibility of the distal lung epithelium to influenza infection and delays the emergence of pro-SPC positive progenitor cells during the repair process. Our findings also shed light on possible approaches to enhance the clinical management of severe influenza pneumonia in the elderly.

【 授权许可】

   
2014 Yin et al.; licensee BioMed Central Ltd.

【 图 表 】

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