Pu Xudong, Li Xin, Cao Lili, Yue Kaiming, Zhao Panpan, Wang Xiaocen, Li Jianhua, Zhang Xichen, Zhang Nan, Zhao Zhiteng, Liang Min, Gong Pengtao
Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.
Department of Parasite, Jilin Academy of Animal Husbandry and Veterinary Medicine, Changchun, China.
Front Cell Dev Biol. 2021 Jul 15;9:694675. doi: 10.3389/fcell.2021.694675. eCollection 2021.
, also known as or , is an important opportunistic, pathogenic, zoonotic, protozoan parasite that infects the small intestines of humans and animals, causing giardiasis. Several studies have demonstrated that innate immunity-associated Toll-like receptors (TLRs) are critical for the elimination of ; however, whether TLR9 has a role in innate immune responses against infection remains unknown. In the present study, various methods, including reverse transcriptase-quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, immunofluorescence, inhibitor assays, and small-interfering RNA interference, were utilized to probe the role of TLR9 in mouse macrophage-mediated defenses against virus (GLV)-free or GLV-containing trophozoites. The results revealed that in stimulated mouse macrophages, the secretion of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-12 p40, was enhanced, concomitant with the significant activation of TLR9, whereas silencing TLR9 attenuated the host inflammatory response. Notably, the presence of GLV exacerbated the secretion of host proinflammatory cytokines. Moreover, stimulation activated multiple signaling pathways, including the nuclear factor κB p65 (NF-κB p65), p38, ERK, and AKT pathways, the latter three in a TLR9-dependent manner. Additionally, inhibiting the p38 or ERK pathway downregulated the -induced inflammatory response, whereas AKT inhibition aggravated this process. Taken together, these results indicated that may induce the secretion of proinflammatory cytokines by activating the p38 and ERK signaling pathways in a TLR9-dependent manner in mouse macrophages. Our findings on the mechanism underlying the TLR9-mediated host inflammatory response may help establish the foundation for an in-depth investigation of the role of TLR9 in the pathogenicity of .
[某种寄生虫名称]，也被称为[其他名称1]或[其他名称2]，是一种重要的机会性致病原生动物寄生虫，属于人畜共患病原体，可感染人类和动物的小肠，引发贾第虫病。多项研究表明，与先天免疫相关的Toll样受体（TLR）对于清除[该寄生虫名称]至关重要；然而，TLR9在针对[该寄生虫名称]感染的先天免疫反应中是否发挥作用仍不清楚。在本研究中，运用了多种方法，包括逆转录定量聚合酶链反应、蛋白质免疫印迹法、酶联免疫吸附测定、免疫荧光法、抑制剂测定以及小干扰RNA干扰，以探究TLR9在小鼠巨噬细胞介导的针对不含[病毒名称]病毒（GLV）或含GLV的[该寄生虫滋养体名称]滋养体的防御中的作用。结果显示，在受到刺激的小鼠巨噬细胞中，促炎细胞因子的分泌增加，包括白细胞介素6（IL - 6）、肿瘤坏死因子α（TNF - α）和IL - 12 p40，同时TLR9显著激活，而沉默TLR9会减弱宿主的炎症反应。值得注意的是，GLV的存在加剧了宿主促炎细胞因子的分泌。此外，[该寄生虫名称]刺激激活了多种信号通路，包括核因子κB p65（NF - κB p65）、p38、ERK和AKT通路，后三条通路以TLR9依赖的方式激活。此外，抑制p38或ERK通路会下调[该寄生虫名称]诱导的炎症反应，而抑制AKT则会加剧这一过程。综上所述，这些结果表明，[该寄生虫名称]可能通过在小鼠巨噬细胞中以TLR9依赖的方式激活p38和ERK信号通路来诱导促炎细胞因子的分泌。我们关于TLR9介导宿主炎症反应机制的研究结果可能有助于为深入研究TLR9在[该寄生虫名称]致病性中的作用奠定基础。
