Francisella tularensis LVS initially activates but subsequently down-regulates intracellular signaling and cytokine secretion in mouse monocytic and human peripheral blood mononuclear cells
Francisella tularensis LVS initially activates but subsequently down-regulates intracellular signaling and cytokine secretion in mouse monocytic and human peripheral blood mononuclear cells
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DOI：
10.1016/j.micpath.2005.02.003
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发表时间：
2005-05-01
影响因子：
3.8
通讯作者：
Sjöstedt, A
中科院分区：
文献类型：
--
作者：
Telepnev, M;Golovliov, I;Sjöstedt, A
单核细胞通过识别保守的病原体成分，构成抵御入侵病原体的重要防御机制。这种识别导致核因子-kappaB(NF-kappa B)和丝裂原活化蛋白激酶(MAPK)等细胞内通路的激活，如c-Jun NH2末端激酶(JNK)和p38。我们发现，在体外感染土拉弗氏菌后，在贴壁的小鼠腹膜细胞、小鼠巨噬细胞系J774A.1、人巨噬细胞系THP-1和人外周血单核细胞中，核因子-kappa B激活，p38和c-jun磷酸化，以及分泌肿瘤坏死因子-α。这发生在感染了人类活疫苗株图拉氏丝虫LVS或名为Delta iglC的突变株(它缺乏23 kDa蛋白的表达)之后，或者在加入了灭活的图拉氏丝虫LVS之后。加入纯化的图拉氏弗氏杆菌脂多糖对细胞无明显影响。当作用持续到5h时，在含有杀灭细菌的培养物或感染Delta iglC菌株的培养物中，激活持续存在。小鼠腹膜细胞、J774细胞和人外周血单核细胞感染后5h内，肿瘤坏死因子-α的信号转导激活和分泌均下调。综上所述，这些结果表明，感染图拉氏F菌活菌可在小鼠和人类细胞中快速诱导促炎反应，但在细菌内化后，这种反应在大多数细胞类型中完全或部分下调。当细胞感染突变的Delta iglC时，这种下调不会发生。(C)2005爱思唯尔有限公司。保留所有权利。
Monocytic cells constitute an important defense mechanism against invading pathogens by recognizing conserved pathogens components. The recognition leads to activation of intracellular pathways involving nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPK), such as the c-Jun NH2-terminal kinase (JNK), and p38. We show that in vitro infection with Francisella tularensis results in activation of NF-kappa B, phosphorylation of p38 and c-Jun, and secretion of TNF-alpha in adherent mouse peritoneal cells, in the mouse macrophage-like cell line J774A.1, in the human macrophage cell line THP-1, and in human peripheral blood monocytic cells. This occurred after infection with the human live vaccine strain, F. tularensis LVS or a mutant strain denoted Delta iglC, which lacks expression of a 23-kDa protein, or after addition of killed F. tularensis LVS. Addition of purified F. tularensis LPS resulted in no discernible effects on the cells. When the effects were followed up to 5 h, activation persisted in cultures with killed bacteria or infected with the Delta iglC strain. In contrast, the signal transduction activation and secretion of TNF-alpha were down-regulated within the 5 h period in mouse peritoneal cells, J774 cells or human peripheral blood mononuclear cells infected with F. tularensis LVS. Together, the results suggest that infection with live F. tularensis LVS bacteria leads to a rapid induction of a proinflammatory response in mouse and human cells but after internalization of bacteria, this response is completely or partly down-regulated in most cell types. This down-regulation does not occur when cells are infected with the mutant Delta iglC. (c) 2005 Elsevier Ltd. All rights reserved.