Conclusion
Our findings demonstrate the crucial role of leukocytes in PALE, shedding light on the development of new host-directed antibacterial therapies and the design of rational dosage regimens.
Methods
Interaction models between bacteria and macrophages were constructed to identify the effects of different antibiotics on the bactericidal activities of macrophages. Oxygen consumption rate, expression of oxidases, and antioxidants were then measured to evaluate the effects of fluoroquinolones (FQs) on the oxidative stress of macrophages. Furthermore, the modulation in endoplasmic reticulum stress and inflammation upon antibiotic treatment was detected to analyze the mechanisms. At last, the peritoneal infection model was utilized to verify the PALE in vivo.
Results
Enrofloxacin significantly reduced the intracellular burden of diverse bacterial pathogens through promoting the accumulation of reactive oxygen species (ROS). The upregulated oxidative response accordingly reprograms the electron transport chain with decreased production of antioxidant enzymes to reduce internalized pathogens. Additionally, enrofloxacin modulated the expression and spatiotemporal localization of myeloperoxidase (MPO) to facilitate ROS accumulation to target invaded bacteria and downregulated inflammatory response to alleviate cellular injury.