RNA-seq of human THP-1 macrophages infected with adherent-invasive E. coli (AIEC) strains

To characterize the host response, we performed RNA-seq profiling of THP-1–derived macrophages infected for 24 h with five distinct AIEC strains, compared to uninfected controls. Transcriptomic analysis revealed extensive reprogramming of macrophage gene expression, marked by activation of pro-inflammatory signaling pathways (NF-κB, JAK–STAT, TNF) and concomitant suppression of lysosome-, phagosome-, and peroxisome-associated programs.

Although pro-death signals were induced, execution modules of apoptosis and ferroptosis remained restrained, consistent with macrophage survival and thus permissive for bacterial replication. A conserved transcriptional signature emerged across strains, characterized by sustained inflammation coupled with diminished antimicrobial capacity. In parallel, we observed strain-specific differences in cytokine expression, lysosomal function, and lipid metabolism, highlighting that macrophage responses vary depending on the infecting AIEC strain.