Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections
Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections
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DOI：
10.1038/nature03408
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发表时间：
2005-03-24
期刊：
影响因子：
64.8
通讯作者：
Bendelac, A
中科院分区：
文献类型：
--
作者：
Mattner, J;DeBord, KL;Bendelac, A
CD1d限制性自然杀伤T（NKT）细胞是一类固有样淋巴细胞，其表达一种保守的T细胞受体，并有助于宿主抵御各种微生物病原体（1,2）。然而，它们的靶脂质抗原一直难以确定。在此我们报道了NKT细胞针对革兰氏阴性、脂多糖（LPS）阴性的α-变形菌（如鼠埃立克体和荚膜鞘氨醇单胞菌）的微生物特异性抗原激活的证据。我们从鞘氨醇单胞菌的细胞壁中鉴定出糖基神经酰胺，其作为小鼠和人类NKT细胞的直接靶标，控制感染小鼠的败血性休克反应和细菌清除。相反，革兰氏阴性、LPS阳性的鼠伤寒沙门氏菌通过识别一种内源性溶酶体鞘糖脂iGb3来激活NKT细胞，该iGb3由LPS激活的树突状细胞呈递。这些发现确定了NKT细胞在抗菌防御中的两个新的抗原靶点，并表明糖基神经酰胺是LPS的一种替代物，用于对革兰氏阴性、LPS阴性细菌细胞壁的固有识别。
CD1d-restricted natural killer T ( NKT) cells are innate-like lymphocytes that express a conserved T-cell receptor and contribute to host defence against various microbial pathogens(1,2). However, their target lipid antigens have remained elusive. Here we report evidence for microbial, antigen-specific activation of NKT cells against Gram-negative, lipopolysaccharide (LPS)negative alpha-Proteobacteria such as Ehrlichia muris and Sphingomonas capsulata. We have identified glycosylceramides from the cell wall of Sphingomonas that serve as direct targets for mouse and human NKT cells, controlling both septic shock reaction and bacterial clearance in infected mice. In contrast, Gram-negative, LPS-positive Salmonella typhimurium activates NKT cells through the recognition of an endogenous lysosomal glycosphingolipid, iGb3, presented by LPS-activated dendritic cells. These findings identify two novel antigenic targets of NKT cells in antimicrobial defence, and show that glycosylceramides are an alternative to LPS for innate recognition of the Gram-negative, LPS-negative bacterial cell wall.