Aging‐related Atg5 defect impairs neutrophil extracellular traps formation

Immunology - Tập 151 Số 4 - Trang 417-432 - 2017
Fengying Xu1,2, Chengmi Zhang3, Zui Zou1, Erica Fan4, Linsong Chen2,5, Yuehua Li2,6, Timothy R. Billiar2,7, Mark A. Wilson2,6, Xueyin Shi1,3, Jie Fan2,7,6
1Department of Anaesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China
2Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA USA
3Department of Anaesthesiology, Shanghai Xinghua Hospital, Jiaotong University School of Medicine, Shanghai, China
4Department of Biological Sciences, University of Pittsburgh School of Arts and Science, Pittsburgh, PA, USA
5Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
6Research and Development, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA
7McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA

Tóm tắt

SummaryFormation of neutrophil extracellular traps (NETs) is an important function of the innate immune system against infections. It has been proven that aging dysregulates immunity and impairs neutrophil function. However, the influence of aging on the ability to produce NETs has yet to be fully addressed. In this study, we tested the hypothesis that a lower level of autophagy in neutrophils from aged mice was responsible for the decrease in NET formation. We demonstrated that a broad range of Toll‐like receptor 2 (TLR2) ligands could efficiently induce reactive oxygen species (ROS) ‐dependent NET release in young mice, but not in aged ones. We further explored that the difference between young and aged mice in TLR2 ligand‐induced NETosis is the result of an Atg5 defect and subsequent impaired autophagy. Furthermore, we found that lower autophagy capacity led to not only reduced NET formation, but also increased apoptosis. Our results suggest an important role of Atg5 and autophagy in maintaining the function of NETs formation in response to infection and in regulating neutrophil death. Targeting autophagy‐promoted NETs may present a therapeutic strategy to improve infection defence in an aged population.

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Immunology

Tập 151 Số 4

417-432

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