Initial delay in the immune response to Francisella tularensis is followed by hypercytokinemia characteristic of severe sepsis and correlating with upregulation and release of damage-associated molecular patterns
Initial delay in the immune response to Francisella tularensis is followed by hypercytokinemia characteristic of severe sepsis and correlating with upregulation and release of damage-associated molecular patterns
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DOI：
10.1128/iai.00215-08
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发表时间：
2008-07-01
影响因子：
3.1
通讯作者：
Teale, Judy M.
中科院分区：
文献类型：
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作者：
Mares, Chris A.;Ojeda, Sandra S.;Teale, Judy M.
“土拉热弗朗西斯菌novicida”鼻内感染在小鼠中引起快速肺炎，用低剂量的细菌（10（2）个细菌）在4 - 6天死亡。死亡时间短表明先天免疫反应失败。由于中性粒细胞通常是第一个浸润感染部位的细胞类型，我们将重点放在这种感染中中性粒细胞的迁移以及参与其招募的细胞因子上。结果表明，嗜中性粒细胞流入F。土拉热亚种novicida感染的小鼠。F.土拉热亚种novicida感染的小鼠与多种促炎细胞因子和趋化因子的上调延迟以及半胱天冬酶-1活化延迟相关。引人注目的是，最初延迟的细胞因子的上调，通过感染后1天，其次是深刻的上调多种细胞因子和趋化因子的水平与严重脓毒症描述的高细胞因子血症一致。这一发现进一步得到了菌血症和高迁移率族蛋白-1和S100 A9的细胞再定位和释放的支持，这两种蛋白都是损伤相关的分子模式分子，已知是严重脓毒症的介质。
"Francisella tularensis subsp. novicida" intranasal infection causes a rapid pneumonia in mice with mortality at 4 to 6 days with a low dose of bacteria (10(2) bacteria). The short time to death suggests that there is a failure of the innate immune response. As the neutrophil is often the first cell type to infiltrate sites of infection, we focused on the emigration of neutrophils in this infection, as well as cytokines involved in their recruitment. The results indicated that there was a significant delay in the influx of neutrophils into the bronchoalveolar lavage fluid of F. tularensis subsp. novicida-infected mice. The delay in neutrophil recruitment in F. tularensis subsp. novicida-infected mice correlated with a delay in the upregulation of multiple proinflammatory cytokines and chemokines, as well as a delay in caspase-1 activation. Strikingly, the initial delay in the upregulation of cytokines through I day postinfection was followed by profound upregulation of multiple cytokines and chemokines to levels consistent with hypercytokinemia described for severe sepsis. This finding was further supported by a bacteremia and the cellular relocalization and release of high-mobility group box-1 and S100A9, both of which are damage-associated molecular pattern molecules and are known to be mediators of severe sepsis.