|
|||||
|
|
The inhibitory receptor CD300a is essential for neutrophil-mediated clearance of urinary tract infection in mice |
|
| Authors: | Batya Isaacson Maya Baron Rachel Yamin Gilad Bachrach Francesca Levi-Schaffer Zvi Granot Ofer Mandelboim |
| Affiliation: | 1. The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, IMRIC, The Hebrew University Medical School, Jerusalem, Israel;2. Department of Developmental Biology and Cancer Research, IMRIC, The Hebrew University Medical School, Jerusalem, Israel;3. The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel;4. Pharmacology and Experimental Therapeutics Unit, School of Pharmacy, Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel These authors contributed equally to this work.;5. Department of Developmental Biology and Cancer Research, IMRIC, The Hebrew University Medical School, Jerusalem, Israel These authors contributed equally to this work. |
| Abstract: | Neutrophils play a crucial role in immune defense against and clearance of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection, the most common bacterial infection in healthy humans. CD300a is an inhibitory receptor that binds phosphatidylserine and phosphatidylethanolamine, presented on the membranes of apoptotic cells. CD300a binding to phosphatidylserine and phosphatidylethanolamine, 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 urinary tract infection. We show that CD300a-deficient neutrophils have impaired phagocytic abilities and despite their increased accumulation at the site of infection, they are unable to reduce bacterial burden in the bladder, which results in significant exacerbation of infection and worse host outcome. Finally, 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. |
| Keywords: | α-hemolysin CD300a Neutrophils Urinary tract infection Epithelial cells |