title: Critical role for CXC ligand 10/CXC receptor 3 signaling in the murine neonatal response to sepsis.
abstract: Previous studies have suggested that neonates rely heavily on innate immunity for their antimicrobial response to bacterial infections. However, the innate immune response by neonates to bacterial infection remains poorly characterized. Here, we show that in a murine model of neonatal polymicrobial sepsis, CXC ligand 10 (CXCL10) concentrations increase in the blood and peritoneum concordant with the peritoneal recruitment of granulocytes and macrophages. Additionally, CXC receptor 3 (CXCR3) expression on elicited peritoneal macrophages and granulocytes increases following sepsis. Blockade of CXCL10 worsens not only recruitment and phagocytic function of peritoneal granulocytes and macrophages but also survival. Deletion of CXCR3 also significantly increases mortality to a septic challenge. Finally, we demonstrate that the protective adjuvant effect of pretreatment with a Toll-like receptor 4 agonist to neonatal sepsis is dependent on an endogenous CXCL10 response and that pretreatment of neonates with CXCL10 can also significantly improve macrophage and granulocyte function and modestly improve outcome to polymicrobial sepsis. Together, these data suggest a critical role for CXCL10 signaling during neonatal sepsis.
authors.affiliation: Departments of Surgery, University of Florida College of Medicine and Dentistry, Gainesville, Florida 32610-0286, USA.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Cuenca
authors.forename: James L
authors.initials: JL
authors.lastname: Wynn
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly-Scumpia
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.forename: Lizette
authors.initials: L
authors.lastname: Vila
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Delano
authors.forename: Clayton E
authors.initials: CE
authors.lastname: Mathews
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallet
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Behrns
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001424:Bacterial Infections / Q000276:immunology* / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D054367:Receptors, CXCR3 / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D051197:Toll-Like Receptor 4