LPS exposure alleviates multiple tissues damage by facilitating macrophage efferocytosis

Toll-like receptors (TLRs) play a crucial role in mediating immune responses by recognizing pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), as well as facilitating apoptotic cell (ACs) clearance (efferocytosis), thus contributing significantly to maintaining homeostasis and promoting tissue resolution. In this study, we investigate the impact of TLR agonists on macrophage efferocytosis. Our findings demonstrate that pretreatment with the TLR agonist lipopolysaccharide (LPS) significantly enhances macrophage phagocytic ability, thereby promoting efferocytosis both in vitro and in vivo. Moreover, LPS pretreatment confers tissue protection against damage by augmenting macrophage efferocytic capacity in murine models. Further examination reveals that LPS modulates efferocytosis by upregulating the expression of Tim4.These results underscore the pivotal role of TLR agonists in regulating the efferocytosis process and suggest potential therapeutic avenues for addressing inflammatory diseases. Overall, our study highlights the intricate interplay between LPS pretreatment and efferocytosis in maintaining tissue homeostasis and resolving inflammation.