Journal Club

PIM1 controls GBP1 activity to limit self-damageand to guard against pathogen infection

Science 2023

Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses.Interferon-g(IFN-g)–inducible antimicrobial factors, such as the guanylate binding proteins (GBPs),promote cell-intrinsic defense by attacking intracellular pathogens and by inducing programmedcell death. Working in human macrophages, we discovered that GBP1 expression in the absence ofIFN-gkilled the cells and induced Golgi fragmentation. IFN-gexposure improved macrophage survivalthrough the activity of the kinase PIM1. PIM1 phosphorylated GBP1, leading to its sequestration by14-3-3s, which thereby prevented GBP1 membrane association. DuringToxoplasma gondiiinfection, thevirulence protein TgIST interfered with IFN-gsignaling and depleted PIM1, thereby increasing GBP1activity. Although infected cells can restrain pathogens in a GBP1-dependent manner, this mechanismcan protect uninfected bystander cells. Thus, PIM1 can provide a bait for pathogen virulence factors,guarding the integrity of IFN-gsignaling