Yang Meimei, Hu Yunhao, Wang Junwei, Zhang Wenlong, Liu Bin
Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China.
Front Immunol. 2025 Jun 11;16:1614952. doi: 10.3389/fimmu.2025.1614952. eCollection 2025.
() is an important opportunistic pathogen in animals and can also cause diseases in humans. Previous studies have shown that infection can upregulate the levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), in host tissues. However, the underlying mechanisms are not yet fully understood. In the current study, we found that both inactivated cells (iTP) and pyolysin (PLO, a major virulence factor of ) can promote the transcription of the IL-1β gene both and . iTP-caused upregulation of IL-1β gene transcription is dependent on nuclear factor-kappa B (NF-κB). On the other hand, we determined that PLO, but not iTP, can promote the maturation of IL-1β by activating caspase-1-mediated processing of pro-IL-1β. Further, we confirmed that PLO can induce potassium ion (K) efflux in mouse macrophages, thereby activating caspase-1 in a Nod-like receptor protein 3 (NLRP3)-dependent manner. Blocking K efflux or knocking down the expression of NLRP3 both inhibited caspase-1 activation and pro-IL-1β processing. Taken together, these findings demonstrate that can promote IL-1β expression at both the transcriptional and post-translational levels in a murine macrophage model. These results significantly enhance our understanding of the pathogenesis of and the interactions between and host immune system.
（某病原体名称）是动物体内一种重要的机会性致病菌，也可导致人类患病。先前的研究表明，该病原体感染可上调宿主组织中促炎细胞因子的水平，如白细胞介素 -1β（IL -1β）。然而，其潜在机制尚未完全明确。在本研究中，我们发现灭活的该病原体细胞（iTP）和溶血素（PLO，该病原体的一种主要毒力因子）均可在体内和体外促进IL -1β基因的转录。iTP引起的IL -1β基因转录上调依赖于核因子 -κB（NF -κB）。另一方面，我们确定PLO而非iTP可通过激活半胱天冬酶 -1介导的前体IL -1β加工过程来促进IL -1β的成熟。此外，我们证实PLO可诱导小鼠巨噬细胞中的钾离子（K⁺）外流，从而以核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）依赖的方式激活半胱天冬酶 -1。阻断K⁺外流或敲低NLRP3的表达均抑制了半胱天冬酶 -1的激活和前体IL -1β的加工。综上所述，这些发现表明该病原体可在小鼠巨噬细胞模型中在转录和翻译后水平促进IL -1β的表达。这些结果显著增强了我们对该病原体发病机制以及该病原体与宿主免疫系统相互作用的理解。
