Amprey Joseph L, Im Jin S, Turco Salvatore J, Murray Henry W, Illarionov Petr A, Besra Gurdyal S, Porcelli Steven A, Späth Gerald F
Department of Medicine, Weill College of Medicine, Cornell University, New York, NY 10021, USA.
J Exp Med. 2004 Oct 4;200(7):895-904. doi: 10.1084/jem.20040704.
Natural killer (NK) T cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. Despite the immunogenicity of microbial lipoglycans and their promiscuous binding to CD1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. In the current work, we show increased susceptibility of NK T cell-deficient CD1d(-/-) mice to Leishmania donovani infection and Leishmania-induced CD1d-dependent activation of NK T cells in wild-type animals. The elicited response was Th1 polarized, occurred as early as 2 h after infection, and was independent from IL-12. The Leishmania surface glycoconjugate lipophosphoglycan, as well as related glycoinositol phospholipids, bound with high affinity to CD1d and induced a CD1d-dependent IFNgamma response in naive intrahepatic lymphocytes. Together, these data identify Leishmania surface glycoconjugates as potential glycolipid antigens and suggest an important role for the CD1d-NK T cell immune axis in the early response to visceral Leishmania infection.
自然杀伤（NK）T细胞可被合成或自身糖脂激活，并参与机体对多种病毒、细菌和原生动物病原体的先天性抵抗。尽管微生物脂聚糖具有免疫原性且能与CD1d广泛结合，但迄今为止，尚未发现通过该途径呈递的病原体衍生糖脂抗原。在当前研究中，我们发现NK T细胞缺陷的CD1d（-/-）小鼠对杜氏利什曼原虫感染的易感性增加，且在野生型动物中，利什曼原虫可诱导NK T细胞发生CD1d依赖性激活。引发的反应呈Th1极化，最早在感染后2小时出现，且不依赖于IL-12。利什曼原虫表面糖缀合物脂磷酸聚糖以及相关的糖基磷脂酰肌醇磷脂与CD1d具有高亲和力结合，并在幼稚肝内淋巴细胞中诱导CD1d依赖性IFNγ反应。这些数据共同表明，利什曼原虫表面糖缀合物是潜在的糖脂抗原，并提示CD1d-NK T细胞免疫轴在内脏利什曼原虫感染早期反应中起重要作用。
