Incomplete autophagy promotes the proliferation of Mycoplasma hyopneumoniae through the JNK and Akt pathways in porcine alveolar macrophages

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.

Immune Evasion of Mycoplasma gallisepticum: An Overview

“…It was reported that M. gallisepticum synthesizes hydrogen peroxide to initiate lipid peroxidation of host cell membrane, thereby compromising the integrity and permeability of the eukaryotic cell membrane and facilitating bacterial entry [ 26 ]. Other mycoplasmas are diverse and may involve cellular pathways or endocytic mechanisms [ 27 , 28 ].…”

Unveiling the stealthy tactics: mycoplasma’s immune evasion strategies

“…M. hyopneumoniae employs the JNK and Akt signaling pathways to induce incomplete autophagy in porcine alveolar macrophages. Incomplete autophagy serves as a defense mechanism, impeding the entry of M. hyopneumoniae into lysosomes and preventing its degradation, allowing the proliferation of M. hyopneumoniae within porcine alveolar macrophages (Wen et al, 2022). Lipid rafts also seem to be involved in mycoplasma invasion, it possibly associated with caveola-dependent endocytosis (Quest et al, 2004).…”