Tong Liu,Yujuan Zhang,Huanjun Zhao,Qi Wu,Jiuqing Xin,Qiao Pan

Infect Immun.2024 Aug 12:e0005124.doi: 10.1128/iai.00051-24.

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.

Keywords: Mycoplasma hyopneumoniae; antiapoptosis; cytokines; polarization; unfolded protein response.