De Chiara Stefania, De Simone Carone Luca, Cirella Roberta, Andretta Emanuela, Silipo Alba, Molinaro Antonio, Mercogliano Marcello, Di Lorenzo Flaviana
Department of chemical sciences, University of Naples Federico II, via Cinthia 4, 80126, Naples, Italy.
CEINGE, Istituto di Biotecnologie avanzate, Via Gaetano Salvatore, 486, 80131, Naples, Italy.
ChemMedChem. 2025 Mar 15;20(6):e202400780. doi: 10.1002/cmdc.202400780. Epub 2025 Jan 15.
With an enormous potential in immunology and vaccinology, lipopolysaccharides (LPSs) are among the most extensively studied bacteria-derived molecules. LPS centered studies are countless, and their results reverberate in all areas of the life sciences, including chemistry, biology, genetics, biophysics, and medicine. Most of these research activities are focused on the LPS-induced immune response activation by means of Myeloid Differentiation protein-2/Toll Like Receptor 4 (MD-2/TLR4) complex, which currently is the most largely explored LPS sensing pathway. However, the enormous structural variability of LPS allows interactions with numerous other receptors involved in a wide range of equally important immunological scenarios. In this review, we explore these additional LPS recognition systems, which operate within interconnected signaling cascades, highlighting their role in maintaining physiological homeostasis and their involvement in the development of severe human diseases. Understanding these pathways, their interconnections, and the crosstalk between them and TLR4/MD-2 is essential for guiding the development of pharmacologically active molecules that could specifically modulate the inflammatory response, paving the way to new strategies for combating immune-mediated diseases and resistant infections.
脂多糖（LPS）在免疫学和疫苗学领域具有巨大潜力，是研究最为广泛的细菌衍生分子之一。以LPS为核心的研究数不胜数，其研究结果在生命科学的各个领域都产生了影响，包括化学、生物学、遗传学、生物物理学和医学。这些研究活动大多聚焦于LPS通过髓样分化蛋白2/ Toll样受体4（MD-2/TLR4）复合物诱导免疫反应激活，这是目前研究最为深入的LPS感知途径。然而，LPS巨大的结构变异性使其能够与众多其他受体相互作用，参与一系列同等重要的免疫反应。在这篇综述中，我们探讨了这些额外的LPS识别系统，它们在相互关联的信号级联中发挥作用，强调它们在维持生理稳态中的作用以及在严重人类疾病发展中的参与情况。了解这些途径、它们之间的相互联系以及它们与TLR4/MD-2之间的相互作用，对于指导能够特异性调节炎症反应的药理活性分子的开发至关重要，为对抗免疫介导疾病和耐药感染的新策略铺平道路。
