Abstract：
Enzootic pneumonia caused by Mycoplasma hyopneumoniae (M. hyopneumoniae) has inflicted substantial economic losses on the global pig industry. The progression of M. hyopneumoniae induced-pneumonia is associated with lung immune cell infiltration and extensive proinflammatory cytokine secretion. Our previous study established that M. hyopneumoniae disrupts the host unfolded protein response (UPR), a process vital for the survival and immune function of macrophages. In this study, we demonstrated that M. hyopneumoniae targets the UPR- and caspase-12-mediated endoplasmic reticulum (ER)-associated classical intrinsic apoptotic pathway to interfere with host cell apoptosis signaling, thereby preserving the survival of host tracheal epithelial cells (PTECs) and alveolar macrophages (PAMs) during the early stages of infection. Even in the presence of apoptosis inducers, host cells infected with M. hyopneumoniae exhibited an anti-apoptotic potential. Further analyses revealed that M. hyopneumoniae suppresses the three UPR branches and their induced apoptosis. Interestingly, while UPR activation typically drives host macrophages toward an M2 polarization phenotype, M. hyopneumoniae specifically obstructs this process to maintain a proinflammatory phenotype in the host macrophages. Overall, our findings propose that M. hyopneumoniae inhibits the host UPR to sustain macrophage survival and a proinflammatory phenotype, which may be implicated in its pathogenesis in inducing host pneumonia.
摘要：
猪肺炎支原体（M.猪肺炎）给全球养猪业造成了巨大的经济损失。猪肺炎支原体肺炎的进展与肺免疫细胞浸润和广泛的促炎细胞因子分泌有关。我们先前的研究确定猪肺炎支原体破坏宿主未折叠蛋白反应（UPR），对巨噬细胞的生存和免疫功能至关重要的过程。在这项研究中,我们证明了猪肺炎支原体靶向UPR和caspase-12介导的内质网（ER）相关的经典内在凋亡途径来干扰宿主细胞凋亡信号，从而在感染的早期阶段保持宿主气管上皮细胞(PTEC)和肺泡巨噬细胞(PAMs)的存活。即使存在凋亡诱导剂，感染猪肺炎支原体的宿主细胞表现出抗凋亡潜能。进一步的分析表明，猪肺炎支原体抑制了三个UPR分支及其诱导的细胞凋亡。有趣的是,而UPR激活通常驱动宿主巨噬细胞向M2极化表型，猪肺炎支原体特异性地阻碍该过程以维持宿主巨噬细胞中的促炎表型。总的来说,我们的发现表明，猪肺炎支原体抑制宿主UPR维持巨噬细胞存活和促炎表型，这可能与其诱发宿主肺炎的发病机理有关。
