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Aging‐related Atg5 defect impairs neutrophil extracellular traps formation
Author(s) -
Xu Fengying,
Zhang Chengmi,
Zou Zui,
Fan Erica K. Y.,
Chen Linsong,
Li Yuehua,
Billiar Timothy R.,
Wilson Mark A.,
Shi Xueyin,
Fan Jie
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12740
Subject(s) - autophagy , atg5 , neutrophil extracellular traps , tlr2 , innate immune system , microbiology and biotechnology , biology , immunology , receptor , reactive oxygen species , extracellular , immune system , apoptosis , function (biology) , inflammation , biochemistry
Summary Formation of neutrophil extracellular traps ( NET s) 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 NET s 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 ( TLR 2) 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 TLR 2 ligand‐induced NET osis 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 NET s formation in response to infection and in regulating neutrophil death. Targeting autophagy‐promoted NET s may present a therapeutic strategy to improve infection defence in an aged population.