Lipopolysaccharide (LPS), a key component of the outer membrane in Gram-negative bacteria (GNB), is widely recognized for its crucial role in mammalian innate immunity and its link to mortality in intensive care units. While its recognition via the Toll-like receptor (TLR)-4 receptor on cell membranes is well established, the activation of the cytosolic receptor caspase-11 by LPS is now known to lead to inflammasome activation and subsequent induction of pyroptosis. Nevertheless, a fundamental question persists regarding the mechanism by which LPS enters host cells. Recent investigations have identified at least four primary pathways that can facilitate this process: bacterial outer membrane vesicles (OMVs); the spike (S) protein of SARS-CoV-2; host-secreted proteins; and host extracellular vesicles (EVs). These delivery systems provide new avenues for therapeutic interventions against sepsis and infectious diseases.

脂多糖 (LPS) 是革兰氏阴性菌 (GNB) 外膜的关键成分，因其在哺乳动物先天免疫中的关键作用及其与重症监护病房死亡率的关系而得到广泛认可。虽然其通过细胞膜上的 Toll 样受体 (TLR)-4 受体进行识别已得到充分证实，但现在已知 LPS 激活胞质受体 caspase-11 会导致炎症小体激活并随后诱导细胞焦亡。然而，关于 LPS 进入宿主细胞的机制仍然存在一个基本问题。最近的研究已经确定了至少四种可以促进这一过程的主要途径：细菌外膜囊泡（OMV）； SARS-CoV-2 的刺突 (S) 蛋白；宿主分泌的蛋白质；和宿主细胞外囊泡（EV）。这些输送系统为脓毒症和传染病的治疗干预提供了新途径。