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Characterization of the NLRP1 inflammasome response in bovine species.
Innate Immunity ( IF 2.8 ) Pub Date : 2019-11-11 , DOI: 10.1177/1753425919886649
Catherine E Vrentas 1 , Paola M Boggiatto 1 , Steven C Olsen 1 , Stephen H Leppla 2 , Mahtab Moayeri 2
Affiliation  

Inflammasomes act as sensors of infection or damage to initiate immune responses. While extensively studied in rodents, understanding of livestock inflammasomes is limited. The NLRP1 inflammasome sensor in rodents is activated by Toxoplasma gondii, Bacillus anthracis lethal toxin (LT), and potentially other zoonotic pathogens. LT activates NLRP1 by N-terminal proteolysis, inducing macrophage pyroptosis and a pro-inflammatory cytokine response. In contrast, NLRP1 in macrophages from humans and certain rodent strains is resistant to LT cleavage, and pyroptosis is not induced. Evolution of NLRP1 sequences towards those leading to pyroptosis is of interest in understanding innate immune responses in different hosts. We characterized NLRP1 in cattle (Bos taurus) and American bison (Bison bison). Bovine NLRP1 is not cleaved by LT, and cattle and bison macrophages do not undergo toxin-induced pyroptosis. Additionally, we found a predicted Nlrp1 splicing isoform in cattle macrophages lacking the N-terminal domain. Resistance to LT in bovine and human NLRP1 correlates with evolutionary sequence similarity to rodents. Consistent with LT-resistant rodents, bovine macrophages undergo a slower non-pyroptotic death in the presence of LPS and LT. Overall, our findings support the model that NLRP1 activation by LT requires N-terminal cleavage, and provide novel information on mechanisms underlying immune response diversity.

中文翻译:

牛种中NLRP1炎性体反应的特征。

炎症小体充当感染或破坏的传感器,以启动免疫反应。虽然在啮齿动物中进行了广泛研究,但对牲畜炎症小体的了解是有限的。啮齿动物中的NLRP1炎症小体传感器被弓形虫,炭疽芽孢杆菌致死毒素(LT)和其他潜在的人畜共患病原体激活。LT通过N端蛋白水解激活NLRP1,诱导巨噬细胞发烧和促炎性细胞因子反应。相反,来自人类和某些啮齿动物品系的巨噬细胞中的NLRP1对LT裂解具有抗性,并且不诱导发烧。NLRP1序列向那些导致细胞凋亡的序列的进化,对于了解不同宿主的先天免疫应答具有重要意义。我们在牛(Bos taurus)和美洲野牛(Bison bison)中鉴定了NLRP1。牛NLRP1不被LT切割,牛和野牛的巨噬细胞不会发生毒素诱导的凋亡。另外,我们在缺乏N末端结构域的牛巨噬细胞中发现了预测的Nlrp1剪接同工型。牛和人NLRP1对LT的抗性与与啮齿类动物的进化序列相似性相关。与耐LT的啮齿动物一致,在LPS和LT的存在下,牛巨噬细胞的非化脓性死亡较慢。总体而言,我们的发现支持了LT激活NLRP1的过程需要N端裂解的模型,并提供了有关免疫应答多样性机制的新信息。与耐LT的啮齿动物一致,在LPS和LT的存在下,牛巨噬细胞的非化脓性死亡较慢。总体而言,我们的发现支持了LT激活NLRP1的过程需要N端裂解的模型,并提供了有关免疫应答多样性机制的新信息。与耐LT的啮齿动物一致,在LPS和LT的存在下,牛巨噬细胞的非化脓性死亡较慢。总体而言,我们的发现支持了LT激活NLRP1的过程需要N端裂解的模型,并提供了有关免疫应答多样性机制的新信息。
更新日期:2019-11-01
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