Zhai Qi-An, Zhang Xi-Chen, Zhang Hong-Bo, Li Jian-Hua, Gong Peng-Tao, Wang Xiao-Cen, Li Xin, Zhang Xu, Zhang Nan
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China.
Parasit Vectors. 2025 Jul 1;18(1):248. doi: 10.1186/s13071-025-06840-w.
Pentatrichomonas hominis (P. hominis) is a newly identified pathogenic zoonotic protozoan belonging to the Trichomonadidae family. P. hominis mainly parasitizes the cecum and colon of humans and other mammals, and it can cause diarrhea. Recently, macrophage extracellular traps (METs) have been shown to play an important role in resistance to parasitic infections. However, it remains unclear whether the release of METs by macrophages contributes to P. hominis resistance, and the underlying mechanism of this association has yet to be elucidated.
Scanning electron microscopy (SEM) and immunofluorescence staining were used to determine whether P. hominis induced the formation of METs in mouse peritoneal macrophages to capture and immobilize the parasite as well as the components of METs, including the DNA backbone, myeloperoxidase (MPO), and histone H3. Reactive oxygen species (ROS) and signaling pathway inhibitor assays revealed that the mechanism of P. hominis-induced MET formation was dependent on nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activation, store-operated calcium entry (SOCE),, and peptidyl arginine deiminase 4 (PAD4) activation. The toll-like receptors 2 (TLR2), extracellular regulated protein kinase 1/2 (ERK1/2) and p38 MAPK signaling pathway were also involved in this process. Trypan blue staining revealed a gradual decrease in the survival rate of P. hominis as the coculture time increased. Trypan blue staining also revealed an increase in the proportion of macrophages.
The results of this study indicate that P. hominis can induce the release of METs via the TLR2/NADPH/PAD4 pathways and that METs have a trapping and killing effect on P. hominis.
This was the first study to reveal that PAD4 and TLR2 were found to be involved in the development of parasite-induced METs, thus providing guidance for further research on the mechanisms of host innate immunity against parasitic infection.
人毛滴虫是一种新发现的致病性人畜共患原生动物，属于毛滴虫科。人毛滴虫主要寄生于人和其他哺乳动物的盲肠和结肠，可引起腹泻。近年来，巨噬细胞胞外诱捕网（METs）已被证明在抵抗寄生虫感染中发挥重要作用。然而，巨噬细胞释放METs是否有助于抵抗人毛滴虫感染，以及这种关联的潜在机制尚待阐明。
采用扫描电子显微镜（SEM）和免疫荧光染色法，检测人毛滴虫是否诱导小鼠腹腔巨噬细胞形成METs，以捕获和固定寄生虫以及METs的成分，包括DNA骨架、髓过氧化物酶（MPO）和组蛋白H3。活性氧（ROS）和信号通路抑制剂试验表明，人毛滴虫诱导MET形成的机制依赖于烟酰胺腺嘌呤二核苷酸磷酸氢（NADPH）氧化酶激活、钙库操纵性钙内流（SOCE）以及肽基精氨酸脱亚氨酶4（PAD4）激活。Toll样受体2（TLR2）、细胞外调节蛋白激酶1/2（ERK1/2）和p38丝裂原活化蛋白激酶信号通路也参与了这一过程。台盼蓝染色显示，随着共培养时间的增加，人毛滴虫的存活率逐渐降低。台盼蓝染色还显示巨噬细胞比例增加。
本研究结果表明，人毛滴虫可通过TLR2/NADPH/PAD4途径诱导METs释放，且METs对人毛滴虫具有捕获和杀伤作用。
这是首次揭示PAD4和TLR2参与寄生虫诱导的METs形成的研究，为进一步研究宿主天然免疫抵抗寄生虫感染的机制提供了指导。
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