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

Adherent-invasive Escherichia coli (AIEC) are associated with Crohn’s disease through their ability to invade, survive, and replicate within intestinal macrophages. 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. Overall, these data reveal that AIEC sustain macrophage inflammatory responses yet restrain cell death and antimicrobial mechanisms, establishing conditions that favor their replication and long-term survival within the host.