Yersinia type three secretion system effectors cooperate to suppress the major immune pathways in primary human macrophages
Numerous bacterial pathogens utilize type 3 secretion systems that inject effector proteins into host immune cells to support their pathogenesis. We investigated the T3SS effectors (Yops) of Yersinia enterocolitica for their individual and combined effects on gene expression, inflammasome formation and Ca2+ signaling in primary human macrophages. The up- or down-regulation of thousands of macrophage genes by Yersinia inflammatory stimuli was effectively suppressed by YopP, which correlated with regulation of histone phosphorylation at H3S10ph, and YopM and YopQ systematically counteracting selected YopP transcriptional effects. Inflammasome formation was reduced by a combination of YopP and YopQ, but not by single effectors or other combinations of them. Intracellular Ca2+ transients were blocked by YopH alone. Thus, the T3SS effectors of Yersinia individually, synergistically or antagonistically suppress the major immune pathways of human macrophages to dampen the immune response.