ABT-263 enhanced bacterial phagocytosis of macrophages in aged mouse through Beclin-1-dependent autophagy

Abstract Background Sepsis is a critical challenge for the older adults as immune function less responsive by aging. Although cell numbers seem preserved in adults, macrophages present age-related decline, which including reduced chemokines, phagocytosis, and autophagy. ABT-263, an inhibitor of anti-apoptotic protein Bcl-2, reported had senolytic effect can selectively clear senescent cells vivo rejuvenate aged tissues. Methods We treated (12–16 months) young (4–6 C57BL/6 mouse with then gave animals cecal slurry injection to induce sepsis observe compound ABT-263 on survival rate sepsis. Additionally, we isolated peritoneal from investigate molecular mechanism. 3-methyladenine (3-MA), phosphatidylinositol 3-kinases (PI3K) inhibitor, rapamycin, autophagy-enhancer, were used block or mimic autophagy, respectively. RT-PCR Western Blot detect autophagy related gene changes EGFP-expressing E. coli was marker evaluate phagocytic ability macrophages. Results The results showed treatment improved while blocking eliminate this effect. It revealed that enhanced increasing Trem-2 receptor. blocked binding Bcl-2 Beclin-1, thus induced Beclin-1-dependent Conclusion macrophage receptors inducing beclin-1-dependent consequently, protected