Card9 protects zymosan-induced peritonitis through regulating autophagy in macrophage

CARD9 is an adapter protein, which plays a critical role in anti-fungal immunity. However, the role of CARD9 in fungal-induced autophagy remains unknown. In this study, we demonstrated that Card9-/- mice displayed more severe phenotype of zymosan-induced peritonitis, presenting as multiple organs injury and increased systemic inflammation. Moreover, the number of macrophage in spleen was increased in Card9-/- mice. Further studies revealed that autophagy was impaired in peritoneal macrophages of Card9-/- -peritonitis mice. Notably, the autophagy agonist, rapamycin, ameliorated peritonitis in Card9-/- mice. Moreover, Card9 mediates the interaction of Malt1 and P62 upon zymosan stimulation. Together, our results confirmed the protective role of Card9 in the development of peritonitis via regulates autophagy in macrophage cells. The study indicates Card9 may be a potential therapeutic target for peritonitis. peritoneal macrophages from wt and card9-/- mice with zymosan treated for 4 hours.