title: Inefficient antimicrobial functions of innate phagocytes render infant mice more susceptible to bacterial infection.
abstract: Neonates and infants, due to the immaturity in their adaptive immunity, are thought to depend largely on the innate immune system for protection against bacterial infection. However, the innate immunity-mediated antimicrobial response in neonates and infants is incompletely characterized. Here, we report that infant mice were more susceptible to microbial sepsis than adult mice, with significantly reduced bacterial clearance from the circulation and visceral organs. Infant PMNs exhibited less constitutive expression of the chemokine receptor CXCR2, and bacterial infection caused further reduction of PMN CXCR2 in infant mice compared with adult mice. This correlates with diminished in vitro chemotaxis of infant PMNs toward the chemoattractant CXCL2 and impaired in vivo recruitment of infant PMNs into the infectious site. Furthermore, consistent with the reduced antimicrobial response in vivo, infant macrophages displayed an impaired bactericidal activity with a defect in phagosome maturation after ingestion of either gram-positive or gram-negative bacteria. Thus, infant mice exhibit an increased vulnerability to microbial infection with delayed bacterial clearance, which is associated with the inefficiency in their innate phagocyte-associated antimicrobial functions characterized by defects in PMN recruitment and macrophage phagosome maturation during microbial sepsis.
authors: Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China.
authors: Qi
authors: Q
authors: Zhang
authors: Andrew P
authors: AP
authors: Coveney
authors: Shenglin
authors: S
authors: Yu
authors: Jing Hua
authors: JH
authors: Liu
authors: Yiping
authors: Y
authors: Li
authors: Siobhan
authors: S
authors: Blankson
authors: H Paul
authors: HP
authors: Redmond
authors: Jiang Huai
authors: JH
authors: Wang
authors: Jian
authors: J
authors: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D004198:Disease Susceptibility; D015870:Gene Expression; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D010588:Phagosomes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D023063:Receptors, Interleukin-8B