Gerber-Tichet Elina, Blanchet Fabien P, Majzoub Karim, Kremer Eric J
Institut de Génétique Moléculaire de Montpellier, Université de Montpellier, CNRS UMR 5535, 34090 Montpellier, France.
Institut de Recherche en Infectiologie de Montpellier, Université de Montpellier, CNRS UMR 9004, 34090 Montpellier, France.
Trends Microbiol. 2025 Jan;33(1):34-47. doi: 10.1016/j.tim.2024.07.001. Epub 2024 Aug 23.
Since the initial description of Toll receptors in Drosophila and their mammalian counterparts Toll-like receptors (TLRs), numerous fundamental and applied studies have explored their crucial role as sensors of pathogen-associated molecular patterns (PAMPs). Among the ten human TLRs, TLR4 is particularly well known for its ability to detect lipopolysaccharides (LPS), a component of the Gram-negative bacterial cell wall. In addition to its archetypal functions, TLR4 is also a versatile virus sensor. This review provides a background on the discovery of TLR4 and how this knowledge laid a foundation for characterization of its diverse roles in antiviral responses, examined through genetic, biochemical, structural, and immunological approaches. These advances have led to a deeper understanding of the molecular functions that enable TLR4 to orchestrate multi-nodal control by professional antigen-presenting cells (APCs) to initiate appropriate and regulated antiviral immune responses.
自从在果蝇中首次描述Toll受体及其哺乳动物对应物Toll样受体(TLR)以来,众多基础研究和应用研究都探讨了它们作为病原体相关分子模式(PAMP)传感器的关键作用。在十种人类TLR中,TLR4因其能够检测脂多糖(LPS)(革兰氏阴性细菌细胞壁的一种成分)而特别知名。除了其原型功能外,TLR4还是一种多功能病毒传感器。本综述提供了TLR4发现的背景知识,以及这些知识如何为通过遗传、生化、结构和免疫学方法研究其在抗病毒反应中的多种作用奠定基础。这些进展使人们对分子功能有了更深入的理解,这些分子功能使TLR4能够通过专业抗原呈递细胞(APC)协调多节点控制,以启动适当且受调节的抗病毒免疫反应。