M1 Macrophage Polarization Is Dependent on TRPC1-Mediated Calcium Entry.

ABSTRACT: Macrophage plasticity is essential for innate immunity, but in-depth signaling mechanism(s) regulating their functional phenotypes are ill-defined. Here we report that interferon (IFN) γ priming of naive macrophages induces store-mediated Ca²⁺ entry and inhibition of Ca²⁺ entry impairs polarization to M1 inflammatory phenotype. In vitro and in vivo functional analyses revealed ORAI1 to be a primary contributor to basal Ca²⁺ influx in macrophages, whereas IFNγ-induced Ca²⁺ influx was mediated by TRPC1. Deficiency of TRPC1 displayed abrogated IFNγ-induced M1 inflammatory mediators in macrophages. In a preclinical model of peritonitis by Klebsiella pneumoniae infection, macrophages showed increased Ca²⁺ influx, which was TRPC1 dependent.

SUBMITTER: Chauhan A 

PROVIDER: S-EPMC6174824 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature