Nonclassical monocyte-derived macrophages are essential for preventing pyelonephritis upon urinary tract infection in mice (P4229)

Abstract

Abstract Phagocytes protect the urinary tract from bacterial infections (UTI). Neutrophils are required early upon infection for clearing off bacteria, however much less is known regarding the function of monocyte-derived macrophages during UTI. Two main subsets of blood monocytes can be distinguished by differential expression of the chemokine receptors CCR2 and CX3CR1. To determine the functional role of monocyte-derived phagocytes, we used CX3CR1 and CCR2 deficient mice and monitored the trafficking of monocyte-derived macrophages during the course of uropathogenic Escherichia coli (UPEC) induced UTI. We found that Ly6+hi/CCR2+hi/CX3CR1+low, classical inflammatory monocytes were recruited from the blood to the bladder and kidney at 8-24h after infection. A subset of Ly6+low/CCR2+low/CX3CR1+hi nonclassical blood monocytes was recruited to urinary organs early (4h) after infection. UPEC induced bacterial burden was significantly elevated in the bladder of CCR2 KO but not CX3CR1 KO mice at 16h post-infection, notoriously, CX3CR1 KO mice were unable to clear UPEC at 48h post-infection; instead, bacteria spread from the bladder to the kidney causing pyelonephritis in these mice but not in WT controls. Our studies indicate that classical monocyte derived macrophages are required to clear bacteria from the bladder during early UTI infection, in contrast, nonclassical macrophages are required for preventing later bacterial spreading, and likely the clearance of bacteria in the kidney.