The innate immune response constitutes the first line of defense against pathogens. It involves the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), the production of inflammatory cytokines and the recruitment of immune cells to infection sites. Recently, ADP-heptose, a soluble intermediate of the lipopolysaccharide biosynthetic pathway in Gram-negative bacteria, has been identified by several research groups as a PAMP. Here, we recapitulate the evidence that led to this identification and discuss the controversy over the immunogenic properties of heptose 1,7-bisphosphate (HBP), another bacterial heptose previously defined as an activator of innate immunity. Then, we describe the mechanism of ADP-heptose sensing by alpha-protein kinase 1 (ALPK1) and its downstream signaling pathway that involves the proteins TIFA and TRAF6 and induces the activation of NF-κB and the secretion of inflammatory cytokines. Finally, we discuss possible delivery mechanisms of ADP-heptose in cells during infection, and propose new lines of thinking to further explore the roles of the ADP-heptose/ALPK1/TIFA axis in infections and its potential implication in the control of intestinal homeostasis.

先天免疫反应构成了抵御病原体的第一道防线。它涉及病原体识别受体（PRR）对病原体相关分子模式（PAMP）的识别、炎症细胞因子的产生以及免疫细胞向感染部位的募集。最近，ADP-庚糖是革兰氏阴性菌脂多糖生物合成途径的可溶性中间体，已被多个研究小组鉴定为PAMP。在这里，我们概括了导致这一鉴定的证据，并讨论了关于 1,7-二磷酸庚糖 (HBP) 免疫原性特性的争议，这是另一种细菌庚糖，之前被定义为先天免疫的激活剂。然后，我们描述了 α 蛋白激酶 1 (ALPK1) 感应 ADP-庚糖的机制及其下游信号通路，该通路涉及蛋白 TIFA 和 TRAF6，并诱导 NF-κB 的激活和炎症细胞因子的分泌。最后，我们讨论了感染过程中ADP-庚糖在细胞中的可能传递机制，并提出了新的思路，以进一步探讨ADP-庚糖/ALPK1/TIFA轴在感染中的作用及其在控制肠道稳态中的潜在意义。