Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China.
Eur J Immunol. 2013 May;43(5):1322-32. doi: 10.1002/eji.201243077. Epub 2013 Mar 22.
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.
新生儿和婴儿由于适应性免疫不成熟，被认为在很大程度上依赖于先天免疫系统来抵御细菌感染。然而，新生儿和婴儿先天免疫介导的抗菌反应尚不完全清楚。在这里，我们报告说，与成年小鼠相比，婴儿小鼠更容易发生微生物败血症，其血液和内脏器官中的细菌清除率明显降低。婴儿 PMN 表现出较低的趋化因子受体 CXCR2 的组成性表达，并且与成年小鼠相比，细菌感染导致婴儿 PMN 的 CXCR2 进一步减少。这与婴儿 PMN 向趋化因子 CXCL2 的体外趋化性降低以及婴儿 PMN 向感染部位的体内募集受损相关。此外，与体内抗菌反应降低一致，婴儿巨噬细胞在吞噬革兰氏阳性或革兰氏阴性细菌后，吞噬体成熟缺陷，表现出杀菌活性受损。因此，与清除细菌的延迟有关，婴儿小鼠表现出对微生物感染的易感性增加，这与先天吞噬细胞相关的抗菌功能效率低下有关，其特征是在微生物败血症期间 PMN 募集和巨噬细胞吞噬体成熟缺陷。
