The inhibitory receptor CD300a is essential for neutrophil-mediated clearance of urinary tract infection in mice.

Neutrophils play a crucial role in immune defense against and clearance of uropathogenic Escherichia coli (UPEC) mediated urinary tract infection (UTI), the most common bacterial infection in healthy humans. CD300a is an inhibitory receptor which binds phosphatidylserine (PS) and phosphatidylethanolamine (PE), presented on the membranes of apoptotic cells. CD300a binding to PS and PE, also known as the 'eat me' signal, mediates immune tolerance to dying cells. Here we demonstrate for the first time that CD300a plays an important role in the neutrophil-mediated immune response to UPEC-induced UTI. We show that CD300a deficient neutrophils have impaired phagocytic abilities and despite their increased accumulation at the site of infection are unable to reduce bacterial burden in the bladder, which results in significant exacerbation of infection and worse host outcome. We demonstrate that UPEC's pore forming toxin α-Hemolysin induces upregulation of the CD300a ligand on infected bladder epithelial cells, signaling to neutrophils to be cleared. This article is protected by copyright. All rights reserved.