Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China.
Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Science, Jilin University, Changchun 130062, Jilin, China.
Vet Parasitol. 2020 Oct;286:109254. doi: 10.1016/j.vetpar.2020.109254. Epub 2020 Sep 22.
Neospora caninum (N. caninum) is an intracellular parasite and is the causative agent of neosporosis, which leads to reproductive failure in cattle. Pyroptosis is a recently discovered form of programmed cell death executed by gasdermin D (GSDMD). This cell death mechanism is an important host defense against intracellular pathogens. However, pyroptosis induced by N. caninum is poorly understood. The aim of this study was to explore the roles of GSDMD-mediated pyroptosis during N. caninum infection in vivo. N. caninum-infected wild type mice and GSDMD-deficient mice were used to evaluate host resistance and its ability to affect immune response against this parasite. The results showed that GSDMD deficiency significantly reduced survival and impaired the host's abilities to clear parasite loads in tissues, monocytes/macrophages and neutrophils. Additionally, GSDMD was essential for circulating IL-18 and IFN-γ production induced by N. caninum infection, indicating that GSDMD can mediate the Th 1 immune response against N. caninum infection. Additional data revealed that treatment with exogenous recombinant IL-18 in N. caninum-infected Gsdmd mice rescues the reduction of circulating IFN-γ production to help eliminate the parasite. Taken together, our data indicate that GSDMD-mediated pyroptosis plays a vital role in maintaining host resistance to N. caninum and is essential for clearing the parasite. This form of programmed cell death promotes the Th 1 immune response by controlling IL-18 release and is considered a host defense against N. caninum. This study expands our understanding of interactions between host immune response/defense and N. caninum infection.
刚地弓形虫（N. caninum）是一种细胞内寄生虫，是引起弓形虫病的病原体，导致牛的繁殖失败。细胞焦亡是一种新发现的由gasdermin D（GSDMD）执行的程序性细胞死亡形式。这种细胞死亡机制是宿主抵抗细胞内病原体的重要防御机制。然而，刚地弓形虫诱导的细胞焦亡机制尚不清楚。本研究旨在探讨 GSDMD 介导的细胞焦亡在刚地弓形虫感染体内的作用。使用刚地弓形虫感染的野生型小鼠和 GSDMD 缺陷型小鼠来评估宿主的抵抗力及其对该寄生虫免疫反应的影响。结果表明，GSDMD 缺陷显著降低了宿主的存活率，削弱了其在组织、单核细胞/巨噬细胞和中性粒细胞中清除寄生虫负荷的能力。此外，GSDMD 对于刚地弓形虫感染诱导的循环 IL-18 和 IFN-γ 的产生是必需的，表明 GSDMD 可以介导针对刚地弓形虫感染的 Th1 免疫反应。额外的数据表明，在刚地弓形虫感染的 Gsdmd 小鼠中用外源性重组 IL-18 治疗可以挽救循环 IFN-γ 产生的减少，有助于消除寄生虫。综上所述，我们的数据表明 GSDMD 介导的细胞焦亡在维持宿主对刚地弓形虫的抵抗力方面起着至关重要的作用，对于清除寄生虫是必需的。这种形式的程序性细胞死亡通过控制 IL-18 的释放来促进 Th1 免疫反应，被认为是宿主对刚地弓形虫的防御机制。本研究扩展了我们对宿主免疫反应/防御与刚地弓形虫感染之间相互作用的理解。
