Yersinia remodels epigenetic histone modifications in human macrophages

Abstract

Various pathogens systematically reprogram gene expression in macrophages, but the underlying mechanisms are largely unknown. We investigated whether the enteropathogen Yersinia enterocolitica alters chromatin states to reprogram gene expression in primary human macrophages. Genome-wide chromatin immunoprecipitation (ChIP) seq analyses showed that pathogen-associated molecular patterns (PAMPs) induced up- or down-regulation of histone modifications (HMod) at approximately 14500 loci in promoters and enhancers. Effectors of Y. enterocolitica reorganized about half of these dynamic HMod, with the effector YopP being responsible for about half of these modulatory activities. The reorganized HMod were associated with genes involved in immune response and metabolism. Remarkably, the altered HMod also associated with 61% of all 534 known Rho GTPase pathway genes, revealing a new level in Rho GTPase regulation and a new aspect of bacterial pathogenicity. Changes in HMod were associated to varying degrees with corresponding gene expression, e. g. depending on chromatin localization and cooperation of the HMod. In summary, infection with Y. enterocolitica remodels HMod in human macrophages to modulate key gene expression programs of the innate immune response.

Live imaging of Yersinia translocon formation and immune recognition in host cells

“…Importantly, in all cases examined, the YopD-ALFA translocon signals occurred after or at the earliest simultaneously with the accumulation of PLCδ1-PH-GFP around the bacteria ( Fig 3E ). To test the spatiotemporal coordination of PIP2 accumulation and translocon formation in physiological target cells of pathogenic yersiniae, we employed primary human macrophages [ 34 ]. Live macrophages expressing PLCδ1-PH-GFP were infected with WA-314 YopD-ALFA in the presence of NbALFA-580 and investigated with live cell imaging.…”