Entamoeba histolytica Induce Signaling via Raf/MEK/ERK for Neutrophil Extracellular Trap (NET) Formation.
Entamoeba histolytica Induce Signaling via Raf/MEK/ERK for Neutrophil Extracellular Trap (NET) Formation.
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DOI：
10.3389/fcimb.2018.00226
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发表时间：
2018
影响因子：
5.7
通讯作者：
Rosales C
中科院分区：
文献类型：
--
作者：
Fonseca Z;Díaz-Godínez C;Mora N;Alemán OR;Uribe-Querol E;Carrero JC;Rosales C
阿米巴病是由溶组织内阿米巴引起的疾病，是寄生虫感染中导致人类死亡的第三大原因。据报道，溶组织内阿米巴与约 1 亿例阿米巴痢疾、结肠炎和阿米巴肝脓肿病例有关，2010 年，这些病例导致全球近 50,000 人死亡。溶组织内阿米巴感染与诱发以大量浸润性中性粒细胞为特征的炎症有关。这些中性粒细胞通过尚未完全描述的机制参与防御这种寄生虫。中性粒细胞的抗菌机制包括吞噬作用、脱颗粒和中性粒细胞胞外陷阱（NET）的形成。最近，我们的小组报告说，NETs 也是响应溶组织内阿米巴滋养体而产生的。但是，NET 的诱导机制仍然未知。在本报告中，我们探讨了溶组织内阿米巴通过类似于 PMA 或 Fc 受体 FcγRIIIb 激活途径的信号传导途径导致 NET 形成的可能性。溶组织阿米巴滋养体刺激中性粒细胞，并评估各种药理学抑制剂对阿米巴诱导的 NET 形成的影响。 Raf、MEK 和 NF-κB 的选择性抑制剂可阻止溶组织内阿米巴诱导的 NET 形成。相反，PKC、TAK1 和 NADPH 氧化酶的抑制剂不会阻止溶组织内阿米巴诱导的 NET 形成。溶组织内阿米巴以 Raf 和 MEK 依赖性方式诱导 ERK 磷酸化。这些数据表明，溶组织内阿米巴激活信号通路诱导 NET 形成，涉及 Raf/MEK/ERK，但它独立于 PKC、TAK1 和活性氧 (ROS)。因此，阿米巴原虫通过与 PMA 或 IgG 受体 FcγRIIIb 激活途径不同的途径激活中性粒细胞。
Amoebiasis, the disease caused by Entamoeba histolytica is the third leading cause of human deaths among parasite infections. E. histolytica was reported associated with around 100 million cases of amoebic dysentery, colitis and amoebic liver abscess that lead to almost 50,000 fatalities worldwide in 2010. E. histolytica infection is associated with the induction of inflammation characterized by a large number of infiltrating neutrophils. These neutrophils have been implicated in defense against this parasite, by mechanisms not completely described. The neutrophil antimicrobial mechanisms include phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Recently, our group reported that NETs are also produced in response to E. histolytica trophozoites. But, the mechanism for NETs induction remains unknown. In this report we explored the possibility that E. histolytica leads to NETs formation via a signaling pathway similar to the pathways activated by PMA or the Fc receptor FcγRIIIb. Neutrophils were stimulated by E. histolytica trophozoites and the effect of various pharmacological inhibitors on amoeba-induced NETs formation was assessed. Selective inhibitors of Raf, MEK, and NF-κB prevented E. histolytica-induced NET formation. In contrast, inhibitors of PKC, TAK1, and NADPH-oxidase did not block E. histolytica-induced NETs formation. E. histolytica induced phosphorylation of ERK in a Raf and MEK dependent manner. These data show that E. histolytica activates a signaling pathway to induce NETs formation, that involves Raf/MEK/ERK, but it is independent of PKC, TAK1, and reactive oxygen species (ROS). Thus, amoebas activate neutrophils via a different pathway from the pathways activated by PMA or the IgG receptor FcγRIIIb.
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影响因子：
3.1
作者：
Asgharpour, A;Gilchrist, C;Houpt, E
通讯作者：
Houpt, E
DOI：
10.1083/jcb.200606027
发表时间：
2007-01-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fuchs TA;Abed U;Goosmann C;Hurwitz R;Schulze I;Wahn V;Weinrauch Y;Brinkmann V;Zychlinsky A
通讯作者：
Zychlinsky A
DOI：
10.4049/jimmunol.1202671
发表时间：
2013-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Byrd AS;O'Brien XM;Johnson CM;Lavigne LM;Reichner JS
通讯作者：
Reichner JS
影响因子：
7.3
作者：
Almyroudis NG;Grimm MJ;Davidson BA;Röhm M;Urban CF;Segal BH
通讯作者：
Segal BH
影响因子：
7.3
作者：
Brinkmann V;Goosmann C;Kühn LI;Zychlinsky A
通讯作者：
Zychlinsky A