Macrophages perform essential functions during bacterial infections, such as phagocytosis of pathogens and neutrophils to reduce spreading of infection, inflammation and tissue damage. The spatial distribution of macrophages is critical to respond to tissue specific adaptations upon infections. Using a novel algorithm for correlative mass spectrometry imaging and state-of-the-art multiplex microscopy, we report here that macrophages within the urinary bladder are positioned in the connective tissue underneath the urothelium. Invading uropathogenic E.coli induced an IL-6-dependent CX3CL1 expression by urothelial cells, facilitating relocation of macrophages from the connective tissue into the urothelium. Those cells phagocytosed UPECs and neutrophils to maintain barrier function of the urothelium, preventing persistent and recurrent urinary tract infection.

Relocation of macrophages maintains the barrier function of the urothelium and protects against persistent infection