Autophagy Is Required for Neutrophil-Mediated Inflammation.
Autophagy, an intracellular degradation and energy recycling mechanism, is emerging as an important regulator of immune responses. However, the role of autophagy in regulating neutrophil functions is not known. We investigated neutrophil biology using myeloid-specific autophagy-deficient mice and found that autophagy deficiency reduced neutrophil degranulation in vitro and in vivo. Mice with autophagy deficiency showed reduced severity of several neutrophil-mediated inflammatory and autoimmune disease models, including PMA-induced ear inflammation, LPS-induced breakdown of blood-brain barrier, and experimental autoimmune encephalomyelitis. NADPH oxidase-mediated reactive oxygen species generation was also reduced in autophagy-deficient neutrophils, and inhibition of NADPH oxidase reduced neutrophil degranulation, suggesting NADPH oxidase to be a player at the intersection of autophagy and degranulation. Overall, this study establishes autophagy as an important regulator of neutrophil functions and neutrophil-mediated inflammation in vivo.
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Abhisek
A
Bhattacharya
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Qin
Q
Wei
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Jin Na
JN
Shin
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Elmoataz
E
Abdel Fattah
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Diana L
DL
Bonilla
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Qian
Q
Xiang
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: teissa@bcm.edu.
N Tony
NT
Eissa
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases