Abstract：
Autophagy is an important conserved homeostatic process related to nutrient and energy deficiency and organelle damage in diverse eukaryotic cells and has been reported to play an important role in cellular responses to pathogens and bacterial replication. The respiratory bacterium Mycoplasma hyopneumoniae has been identified to enter porcine alveolar macrophages, which are considered important immune cells. However, little is known about the role of autophagy in the pathogenesis of M. hyopneumoniae infection of porcine alveolar macrophages. Our experiments demonstrated that M. hyopneumoniae infection enhanced the formation of autophagosomes in porcine alveolar macrophages but prevented the fusion of autophagosomes with lysosomes, thereby blocking autophagic flux and preventing the acidification and destruction of M. hyopneumoniae in low-pH surroundings. In addition, using different autophagy regulators to intervene in the autophagy process, we found that incomplete autophagy promoted the intracellular proliferation of M. hyopneumoniae. We also found that blocking the phosphorylation of JNK and Akt downregulated the autophagy induced by M. hyopneumoniae, but pathways related to two mitogen-activated protein kinases (Erk1/2 and p38) did not affect the process. Collectively, M. hyopneumoniae induced incomplete autophagy in porcine alveolar macrophages through the JNK and Akt signalling pathways; conversely, incomplete autophagy prevented M. hyopneumoniae from entering and degrading lysosomes to realize the proliferation of M. hyopneumoniae in porcine alveolar macrophages. These findings raise the possibility that targeting the autophagic pathway may be effective for the prevention or treatment of M. hyopneumoniae infection.
摘要：
自噬是一种重要的保守的稳态过程，与多种真核细胞的营养和能量缺乏以及细胞器损伤有关，据报道，自噬在细胞对病原体的反应和细菌复制中起重要作用。猪肺炎支原体呼吸道细菌已被鉴定进入猪肺泡巨噬细胞，被认为是重要的免疫细胞。然而,自噬在猪肺炎支原体感染猪肺泡巨噬细胞发病机制中的作用鲜为人知。我们的实验表明，猪肺炎支原体感染增强了猪肺泡巨噬细胞自噬体的形成，但阻止了自噬体与溶酶体的融合，从而阻断自噬通量并防止猪肺炎支原体在低pH环境中的酸化和破坏。此外,使用不同的自噬调节因子干预自噬过程，我们发现不完全自噬促进猪肺炎支原体细胞内增殖。我们还发现阻断JNK和Akt的磷酸化下调猪肺炎支原体诱导的自噬,但是与两种丝裂原激活的蛋白激酶（Erk1/2和p38）相关的途径并不影响该过程。总的来说，猪肺炎支原体通过JNK和Akt信号通路诱导猪肺泡巨噬细胞不完全自噬；相反，不完全自噬阻止猪肺炎支原体进入和降解溶酶体，实现猪肺炎支原体在猪肺泡巨噬细胞中的增殖。这些发现提高了靶向自噬途径可能有效预防或治疗猪肺炎支原体感染的可能性。
