LAP inhibits the clearance of Staphylococcus aureus by neutrophils and suppressed excessive inflammatory responses in mice.

Staphylococcus aureus (S. aureus) is a major cause of acute pneumonia, which leads to various complications, including lung abscess, respiratory distress syndrome, and myocarditis. With the rapid development of drug resistance, it is urgent to find new strategies for the treatment of S. aureus infectious diseases. The LC3-associated phagocytosis (LAP) has been reported to play a defensive role in various bacterial infections. However, certain pathogens have evolved strategies to resist LAP and even utilize the LAP effect exerted by the host for bacterial reproduction. In this article, we demonstrated that during the acute pulmonary infection caused by S. aureus, the LAP function is detrimental to the host's ability to eliminate the bacteria. LAP hinders the bactericidal effect of neutrophils by inhibiting the production of ROS, the secretion of NO, and the degranulation of cells. However, LAP helps to control the excessive inflammation in the host. The LAP effects of neutrophils and macrophages inhibit the inflammatory response through the MAPK and NF-κB pathways. These data suggest that targeting LAP may become a promising new treatment for S. aureus infections.