Palaniyar Nades, Nadesalingam Jeya, Reid Kenneth B M
Department of Biochemistry, Oxford University, United Kingdom.
Immunobiology. 2002 Sep;205(4-5):575-94. doi: 10.1078/0171-2985-00156.
The two major gram-positive bacterial (GPB) ligands are peptidoglycan (PGN) and lipoteichoic acid (LTA). These polymeric LTA and highly organized PGN contain repeating carbohydrate moieties, which are potential targets for pattern recognition molecules. The major pattern recognition proteins and receptors, which bind GPB, either have a lectin, PGN recognition, collagen or leucine-rich repeat (LRR) domain. The soluble innate immune proteins (IIPs) that bind to PGN and LTA include pulmonary collectins surfactant-associated proteins (SP-) A and D, lectin-like pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP), and sCD14. Membrane-anchored lectin or lectin-like group members include macrophage mannose receptor (MR), complement receptor 3 (CR3, or Mac-1, or integrin CD11b/CD18), scavenger receptor A (SRCL-1), lectin-like oxidized LDL receptor 1 (LOX-1), and GPI-anchored CD14. Although Toll-like receptor (TLR) 2 and 4, and CD14 contain extracellular LRR domains, only TLRs have a cytoplasmic domain for signal transduction. Three of the four recently discovered human PGN recognition proteins (PGRP) have a transmembrane domain, and hence, considered as true receptors for GPB. Since lysozyme is the only known pulmonary enzyme that can lyse bacterial cell wall PGN, other innate immune molecules appear to be responsible for signalling and enhancing the clearance of GPB infection from the lung. Interestingly, pulmonary collectins bind not only to GPB ligands but also to the receptors, CD14 and TLR, and antigen processing cells such as dentritic cells. These complex interactions appear to play major roles in linking innate and adaptive immunity, and maintaining a pathogen-free lung with minimal, or no inflammation.
两种主要的革兰氏阳性菌（GPB）配体是肽聚糖（PGN）和脂磷壁酸（LTA）。这些聚合的LTA和高度有序的PGN含有重复的碳水化合物部分，它们是模式识别分子的潜在靶点。与GPB结合的主要模式识别蛋白和受体，要么具有凝集素、PGN识别、胶原蛋白或富含亮氨酸重复序列（LRR）结构域。与PGN和LTA结合的可溶性固有免疫蛋白（IIP）包括肺凝集素表面活性物质相关蛋白（SP-）A和D、凝集素样五聚体C反应蛋白（CRP）和血清淀粉样P成分（SAP），以及可溶性CD14。膜锚定凝集素或凝集素样家族成员包括巨噬细胞甘露糖受体（MR）、补体受体3（CR3，或Mac-1，或整合素CD11b/CD18）、清道夫受体A（SRCL-1）、凝集素样氧化型低密度脂蛋白受体1（LOX-1）和糖基磷脂酰肌醇锚定的CD14。虽然Toll样受体（TLR）2和4以及CD14含有细胞外LRR结构域，但只有TLR具有用于信号转导的细胞质结构域。最近发现的四种人类PGN识别蛋白（PGRP）中有三种具有跨膜结构域，因此被认为是GPB的真正受体。由于溶菌酶是唯一已知的可裂解细菌细胞壁PGN的肺酶，其他固有免疫分子似乎负责信号传导并增强从肺部清除GPB感染的能力。有趣的是，肺凝集素不仅与GPB配体结合，还与受体CD14和TLR以及抗原处理细胞如树突状细胞结合。这些复杂的相互作用似乎在连接固有免疫和适应性免疫以及维持肺部无病原体且炎症最小或无炎症方面发挥着主要作用。
