Drug resistance is a growing problem that necessitates new strategies to combatpathogens. Neutrophil phagocytosis and production of intracellular ROS, in particular, has been shown to cooperate with antibiotics in the killing of microbes. This studytested the hypothesis that p85α, the regulatory subunit of PI3K, regulates productionof intracellular ROS. Genetic knockout of p85α in mice caused decreased expression of catalytic subunits p110α, p110β p110γ, but did not change expression levelsof the NADPH oxidase complex subunits p67phox, p47phox, and p40phox. When p85α ,p55α, and p50α (all encoded by Pik3r1) were deleted, there was an increase inintracellular ROS with no change in phagocytosis in response to both Fcγ receptorand complement receptor stimulation. Furthermore, the increased intracellular ROS correlated with significantly improved neutrophil killing of both methicillin-susceptibleand methicillin-resistant S. aureus. Our findings suggest inhibition of p85α as novel approach to improving the clearance of resistant pathogens.
- Immune response
- Immunology and Microbiology Section
- NADPH oxidase
ASJC Scopus subject areas