Baz Ahmed Adel, Chen Shengli, Hao Huafang, Jin Xiangrui, Lan Shimei, Li Zhangcheng, Jin Shanyu, Zhang Yifan, Chu Yuefeng
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, China.
FASEB J. 2024 Dec 15;38(23):e70238. doi: 10.1096/fj.202402304R.
Mycoplasma bovis has emerged as a significant pathogen in cattle, leading to considerable economic losses in the cattle industry. It is associated with various clinical syndromes, including pneumoniae, mastitis, and arthritis. The innate immune response, particularly macrophages, plays a crucial role in combating infections caused by such pathogens. The release of macrophage extracellular traps (METs) represents a novel defense mechanism employed by macrophages; however, the impact of M. bovis on the formation of METs in bovine macrophages remains unknown. Therefore, the primary objective of this study is to investigate the mechanism by which M. bovis affects the formation of bovine METs and to evaluate their bactericidal efficacy. Our findings revealed that the bovine macrophage cell lines released DNA fibrils that colocalized with histones and cellular proteins in response to M. bovis infection, as visualized by confocal and scanning electron microscopy. Moreover, the formation of METs was found to depend on NADPH oxidase, which is crucial for reactive oxygen species generation. Importantly, the formation of METs led to cell lysis in response to M. bovis infection, as indicated by the release of lactate dehydrogenase, and this process was found to be independent of apoptosis and pyroptosis. Moreover, the release of METs in response to M. bovis infection was effective in both killing and restricting its growth. Overall, our study first described how METs were produced in bovine macrophages that responded to M. bovis and demonstrated their significant function in bacterial killing, which is helpful to improve our understanding of the host's immune defense against this pathogen.
牛支原体已成为牛群中的一种重要病原体，给养牛业造成了相当大的经济损失。它与多种临床综合征有关，包括肺炎、乳腺炎和关节炎。先天性免疫反应，尤其是巨噬细胞，在对抗此类病原体引起的感染中起着关键作用。巨噬细胞胞外陷阱（METs）的释放是巨噬细胞采用的一种新型防御机制；然而，牛支原体对牛巨噬细胞中METs形成的影响仍不清楚。因此，本研究的主要目的是探讨牛支原体影响牛METs形成的机制，并评估其杀菌效果。我们的研究结果表明，通过共聚焦显微镜和扫描电子显微镜观察，牛巨噬细胞系在感染牛支原体后释放出与组蛋白和细胞蛋白共定位的DNA纤维。此外，发现METs的形成依赖于NADPH氧化酶，这对活性氧的产生至关重要。重要的是，如乳酸脱氢酶的释放所示，METs的形成导致细胞在感染牛支原体后裂解，并且发现这个过程与凋亡和焦亡无关。此外，感染牛支原体后METs的释放对杀死和限制其生长均有效。总体而言，我们的研究首次描述了牛巨噬细胞在对牛支原体作出反应时如何产生METs，并证明了它们在细菌杀伤中的重要功能，这有助于提高我们对宿主针对这种病原体的免疫防御的理解。
