Lipopolysaccharide preconditioning augments the antibacterial activity of renal macrophages and ameliorates acute kidney injury caused by <i>Staphylococcus aureus</i> bacteremia in mice

IntroductionRepeated injections of low-dose lipopolysaccharide (LPS preconditioning) augment the antibacterial activity of liver macrophages. In this study, a mouse model of acute kidney injury (AKI) induced by <i>Staphylococcus aureus (S. aureus)</i> bacteremia was used to investigate the effects of LPS preconditioning on renal macrophages.MethodsEight-week-old C57BL/6J mice were preconditioned with either low-dose LPS (5 μg/kg) or the vehicle for three consecutive days. Kidney immune cells were isolated, and the antibacterial activity of renal macrophages was assessed by pHrodo^TM-labeled <i>S. aureus in vitro</i>. Twenty-four hours after the last LPS injection, the mice were intravenously challenged with <i>S. aureus</i> (2 × 10⁷ CFU) and their renal function was evaluated to identify the changes.ResultsMouse renal macrophages exhibited a weak antibacterial activity against <i>S. aureus</i> compared with the liver and spleen macrophages. LPS preconditioning elevated the count of F4/80^low CD11b^high bone marrow-derived macrophages (BMDM) and augmented their antibacterial activities in the mouse kidney. It also enhanced the antibacterial activity of F4/80^high CD11b^low tissue-resident macrophages (TRM) without altering their abundance. LPS preconditioning lowered the bacterial propagation in the kidney in the challenged mice and ameliorated sepsis-associated AKI compared with the control. LPS preconditioning upregulated the CD80/CD206 expression (M1/M2) ratio in BMDMs in the kidney before bacterial challenge and reduced their M1/M2 ratio following <i>S. aureus</i> challenge compared with the control.ConclusionLPS preconditioning enhanced the antibacterial activity of the renal macrophages against <i>S. aureus</i> and suppressed the excessive activation of M1 macrophages following <i>S. aureus</i> challenge, resulting in the amelioration of AKI caused by <i>S. aureus</i> bacteremia.