STIM1-mediated calcium influx controls antifungal immunity and the metabolic function of Th17 cells

ABSTRACT: Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca2+ influx in immune cells is mediated by stromal interaction molecule 1 (STIM1) and its activation of the Ca2+ channel ORAI1. We here identify patients with a novel mutation in STIM1 (p.L374P) that abolishes Ca2+ influx and results in increased susceptibility to fungal and other infections. In mice, deletion of STIM1 in all immune cells enhanced susceptibility to mucosal C. albicans infection, whereas T cell-specific deletion of STIM1 impaired immunity to systemic C. albicans infection. STIM1 deletion impaired the expression of Th17 cytokines essential for antifungal immunity and compromised the expression of genes in several metabolic pathways including Foxo and HIF1? signal

SUBMITTER: Dr. Sascha Kahlfuss 

PROVIDER: S-SCDT-EMM-2019-11592 | biostudies-other |

REPOSITORIES: biostudies-other