Uropathogenic Escherichia coli causes cortical tubular necrotic cell death and the release of macrophage migration inhibitory factor

The macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is deregulated in acute kidney injury (AKI) through an unknown mechanism. In the present study, we used a previously described mouse model of ascending urinary tract infection in which uropathogenic Escherichia coli (UPEC) were transurethrally inoculated to induce kidney infections. Here, we show that urinary MIF was upregulated during AKI while MIF was abundantly expressed in the renal cortical tubules and that UPEC infection caused a decrease in tubular MIF. Infections with UPEC in vitro caused MIF release in a cell type-dependent manner, which was independent of receptor-mediated internalization, signal transduction, and transcription. Indeed, UPEC infection-induced necrotic cell death in vitro and in vivo correlated with extracellular acidification and processed MIF secretion. These data suggest that MIF is released by necrotic renal cortical tubular cells during UPEC infection.

► This study investigates MIF release in vivo and in vitro under UPEC infection. ► MIF is abundantly expressed in the renal cortical tubules. ► Urinary tract infection of UPEC causes urinary production of MIF. ► UPEC in vitro causes MIF release from renal cortical tubular cells. ► UPEC causes necrotic cell death in vitro and in vivo and processes MIF secreting.