Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis.
Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis.
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DOI：
10.1038/s41598-021-92001-9
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发表时间：
2021-06-16
影响因子：
4.6
通讯作者：
Sharma J
中科院分区：
文献类型：
--
作者：
Chauhan A;Sharma A;Tripathi JK;Sun Y;Sukumran P;Singh BB;Mishra BB;Sharma J
尽管具有保护性抗菌功能，中性粒细胞胞外陷阱（NETs）在包括败血症在内的几种疾病条件下与炎症反应的传播有关。在这种炎症条件下产生的高度扩散的外源性ROS可以诱导旺盛的NETs，因此在炎症性疾病中需要抑制NETs。在这里，我们报道了被称为寄生配体（PL）的寄生虫排泄/分泌因子通过阻断非选择性钙渗透通道瞬时受体电位美拉他汀2 （TRPM2）的激活来抑制ros诱导的NETs。在化脓性腹膜炎的临床前模型中测试了PL介导的阻断NET形成的治疗意义，其中PL治疗调节中性粒细胞死亡模式，包括NET形成和减轻中性粒细胞介导的炎症反应。这转化为提高存活率，减少感染小鼠的全身和局部细菌负荷。总之，我们的研究结果表明PL是中性粒细胞功能的重要生物学调节剂，与包括腹膜炎在内的多种炎症性疾病有关。
Despite their protective antimicrobial function, neutrophil extracellular traps (NETs) have been implicated in propagation of inflammatory responses in several disease conditions including sepsis. Highly diffusible exogenous ROS produced under such inflammatory conditions, can induce exuberant NETs, thus making inhibition of NETs desirable in inflammatory diseases. Here we report that helminth parasite excretory/secretory factors termed as parasitic ligands (PL) inhibit ROS-induced NETs by blocking the activation of nonselective calcium permeable channel Transient Receptor Potential Melastatin 2 (TRPM2). Therapeutic implication of PL mediated blockage of NET formation was tested in preclinical model of septic peritonitis, where PL treatment regulated neutrophil cell death modalities including NET formation and mitigated neutrophil mediated inflammatory response. This translated into improved survival and reduced systemic and local bacterial load in infected mice. Overall, our results posit PL as an important biological regulator of neutrophil functions with implications to a variety of inflammatory diseases including peritonitis.
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影响因子：
5.8
作者：
Chauhan A;Sun Y;Sukumaran P;Quenum Zangbede FO;Jondle CN;Sharma A;Evans DL;Chauhan P;Szlabick RE;Aaland MO;Birnbaumer L;Sharma J;Singh BB;Mishra BB
通讯作者：
Mishra BB
DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
5.5
作者：
Itakura, Asako;McCarty, Owen J. T.
通讯作者：
McCarty, Owen J. T.
影响因子：
7.3
作者：
Kimball AS;Obi AT;Diaz JA;Henke PK
通讯作者：
Henke PK