Murine neonates infected with Yersinia enterocolitica develop rapid and robust proinflammatory responses in intestinal lymphoid tissues.
Murine neonates infected with Yersinia enterocolitica develop rapid and robust proinflammatory responses in intestinal lymphoid tissues.
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感染小肠结肠炎耶尔森氏菌的小鼠新生儿在肠道淋巴组织中产生快速而强烈的促炎反应。
DOI：
10.1128/iai.01489-13
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发表时间：
2014
影响因子：
3.1
通讯作者：
Adkins,Becky
中科院分区：
文献类型：
--
作者：
Siefker,DavidT;Echeverry,Andrea;Brambilla,Roberta;Fukata,Masayuki;Schesser,Kurt;Adkins,Becky
新生动物通常很容易受到细菌病原体的感染。然而，我们最近报道了新生小鼠对肠道结肠炎耶尔森菌感染具有高度抗性。在这里，我们表明，在新生儿的肠系膜淋巴结（MLN）中，促炎反应大大超过成人。早在感染后18小时，新生儿MLN中就出现了促炎基因的高水平诱导表达。随后在感染后24小时检测到明显的先天吞噬细胞募集。酶联免疫吸附斑点试验（ELISPOT）分析表明，新生儿MLN炎症增强的部分原因是促炎细胞因子分泌细胞的频率增加。此外，CD11b+和CD11b -细胞群似乎都在促炎基因表达中发挥作用。新生儿MLN的炎症水平也依赖于关键的细菌成分。缺乏毒力质粒的小肠结肠炎菌未能诱导先天吞噬细胞募集。相比之下，在感染ayopp缺陷菌株的新生儿MLN中，肿瘤坏死因子α (TNF-α)蛋白表达和中性粒细胞募集明显高于野生型小肠结肠炎耶氏菌，而在成人中仅略有增加。这种高炎症反应与新生儿脾脏的定植和更高的死亡率有关，而成人的死亡率没有差异。该模型强调了肠道淋巴组织炎症的动态水平，并揭示了新生儿炎症的保护性（野生型菌株）和有害（yopp缺陷菌株）后果。此外，这些结果表明，新生儿肠淋巴组织在应对细菌性肠病原体感染时具有快速调动先天成分的巨大潜力。
Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+and CD11b−cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with ayopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens.