The IRE1α Stress Signaling Axis Is a Key Regulator of Neutrophil Antimicrobial Effector Function.

ABSTRACT: Activation of the endoplasmic reticulum stress sensor, IRE1α, is required for effective immune responses against bacterial infection and is associated with human inflammatory diseases in which neutrophils are a key immune component. However, the specific role of IRE1α in regulating neutrophil effector function has not been studied. In this study, we show that infection-induced IRE1α activation licenses neutrophil antimicrobial capacity, including IL-1β production, formation of neutrophil extracellular traps (NETs), and methicillin-resistant Staphylococcus aureus (MRSA) killing. Inhibition of IRE1α diminished production of mitochondrial reactive oxygen species and decreased CASPASE-2 activation, which both contributed to neutrophil antimicrobial activity. Mice deficient in CASPASE-2

SUBMITTER: Abuaita BH 

PROVIDER: S-EPMC8683563 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature