Mycoplasma bovis activates apoptotic caspases to suppress xenophagy for its intracellular survival.

Mammalian caspases are categorized into apoptotic and inflammatory types. Apoptotic caspases mediate apoptosis activation, while inflammatory caspases participate in inflammasome activation. Previous studies have shown that apoptotic caspases regulate autophagy in both cancer and pharmacological treatment models. However, the relationship between apoptotic caspases and xenophagy during pathogen infection remains elusive. In the current study, we used Mycoplasma bovis (M. bovis) as a model pathogen investigating the relationship between apoptotic caspases and xenophagy during infection. We found that M. bovis activated apoptotic caspases by triggering mitochondrial damage in macrophages, and the intracellular survival of M. bovis was enhanced by the activation of apoptotic caspases and restricted by the inhibition of apoptotic caspases. Moreover, confocal microscopy and Western blot analysis revealed that the activation of apoptotic caspases impedes host xenophagy by cleaving autophagy-related protein Beclin 1. Our findings indicate that M. bovis utilizes host apoptotic caspases to suppress xenophagy, thereby enhancing its intracellular survival. This research contributes to understanding the interplay between apoptotic caspases and xenophagy during pathogen infection, offering novel insights into the intracellular survival mechanisms of mycoplasma in macrophages.