Role of neutrophils and macrophages in the pathogenesis of necrotizing enterocolitis caused by Cronobacter sakazakii.
Role of neutrophils and macrophages in the pathogenesis of necrotizing enterocolitis caused by Cronobacter sakazakii.
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DOI：
10.1016/j.jss.2011.04.019
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Prasadarao NV
中科院分区：
文献类型：
--
作者：
Emami CN;Mittal R;Wang L;Ford HR;Prasadarao NV
阪崎慢杆菌(Cronbacter sakazakii，CS)是一种高毒力的革兰氏阴性条件致病菌，与坏死性小肠结肠炎(NEC)的临床暴发有关。粘膜免疫细胞在CS感染中的作用尚不清楚。在这项研究中，我们试图通过一种新的新生小鼠模型来阐明中性粒细胞(中性粒细胞)和巨噬细胞在CS诱导的NEC发病中的作用。分别用Gr-1抗体和卡拉胶去除新生小鼠的中性粒细胞和巨噬细胞，然后感染103CFU的CS。病理学家根据肠道的形态变化对这些小鼠的NEC的发育进行了评估。用酶联免疫吸附试验检测感染小鼠血清和肠匀浆中细胞因子的产生。流式细胞仪检测诱导型一氧化氮合酶(INOS)的表达，Greiss法检测一氧化氮(NO)的产生。与野生型小鼠相比，新生小鼠感染CS后，中性粒细胞和巨噬细胞的耗尽导致树突状细胞(DC)在肠道中的募集增加。与饲喂CS的野生型小鼠相比，PMN和巨噬细胞耗竭小鼠的肠道细菌载量、促炎细胞因子的产生、iNOS表达和NO产生增加。此外，与感染CS的野生型小鼠相比，感染前PMN和巨噬细胞的耗尽会导致严重的炎症、绒毛破坏和肠道细胞凋亡增加。我们的数据表明，PMN和巨噬细胞在固有层(LP)的耗竭加剧了实验性NEC，表明这两种免疫细胞在感染初期对CS的清除起着重要作用。在没有这些免疫细胞的情况下，粘膜细胞因子反应的增加和NO的产生可能是观察到的粘膜损伤增加的原因。了解CS是如何利用本研究中报道的新型NEC小鼠模型操纵这些细胞的，将为开发新的治疗和预防策略来对抗NEC提供重要的启示。
Cronobacter sakazakii (CS) is a highly virulent gram-negative opportunistic pathogen that has been implicated in clinical outbreaks of necrotizing enterocolitis (NEC). The role of mucosal immune cells in CS infection is not well understood. In this study, we sought to elucidate the role of neutrophils (polymorphonuclear leukocytes; PMNs) and macrophages in the pathogenesis of NEC induced by CS using a novel newborn mouse model. PMNs and macrophages were depleted in newborn mice using Gr-1 antibody and carrageenan respectively, and then infected with 103 CFU of CS. The development of NEC in these mice was assessed by a pathologist based on the morphological changes in the intestine. Cytokine production was determined in the serum and intestinal homogenates of infected mice by ELISA. Inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production was determined by flow cytometry and Greiss method, respectively. Depletion of PMNs and macrophages in newborn mice led to increased recruitment of dendritic cells (DCs) in the intestine compared to wild-type mice upon infection with CS. PMN- and macrophage-depleted mice showed increased bacterial load, production of pro-inflammatory cytokines, iNOS expression and NO production in the intestines in comparison to wild-type mice fed with CS. In addition, depletion of PMNs and macrophages prior to infection in mice resulted in severe inflammation, villus destruction and enhanced enterocyte apoptosis in the intestines compared to CS-infected wild-type mice. Our data suggest that depletion of PMNs and macrophages from the lamina propria (LP) exacerbates experimental NEC, indicating that both of these immunocytes play an important role in the clearance of CS during the initial stages of infection. The increased mucosal cytokine response and NO production in the absence of these immunocytes may be responsible for the observed increase in mucosal injury. Understanding how CS manipulates these cells employing novel mouse model of NEC reported in this study will provide significant insights for the development of novel therapeutic and preventive strategies to combat NEC.
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DOI：
10.1038/labinvest.2008.164
发表时间：
2009-03
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6
作者：
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通讯作者：
Prasadarao, Nemani V.
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影响因子：
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Ford, HR
影响因子：
2
作者：
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