NKT cells mediate organ-specific resistance against Leishmania major infection
NKT cells mediate organ-specific resistance against Leishmania major infection
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DOI：
10.1016/j.micinf.2005.07.002
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发表时间：
2006-02-01
影响因子：
5.8
通讯作者：
Bogdan, C
中科院分区：
文献类型：
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作者：
Mattner, J;Donhauser, N;Bogdan, C
虽然获得性T细胞介导的对细胞内病原体如利什曼原虫的保护在过去已经得到了很好的研究，但涉及其先天控制的细胞和机制仍然知之甚少。在这里，我们研究了自然杀伤T（NKT）细胞在高剂量L。主要小鼠感染模型。试管湖（L. major仅弱刺激NKT细胞并拮抗其对原型NKT细胞配体α-半乳糖神经酰胺的反应，表明L.主要部分逃避NKT细胞的活化。通过皮下感染Ja 281（-/-）小鼠分析的NKT细胞缺乏（缺乏恒定的CD 1d限制性NKT细胞）和CD 1（-/-）小鼠（缺乏所有CD 1d限制性NKT细胞）导致皮肤病变的短暂增加，但不损害感染的临床治愈、NK细胞细胞毒性、IFN-γ的产生、诱导型一氧化氮合酶的表达，以及控制淋巴结中的寄生虫。然而，在脾脏中，NK细胞毒性和早期IFN-γ产生需要NKT细胞，它们降低了寄生虫负荷，并对利什曼原虫抗原特异性T细胞应答产生旁观者效应，最明显的是在全身感染后。因此，NKT细胞在感染L.主要的，但不是必需的寄生虫控制。(c)2005年，Elsevier SAS。All rights reserved.
Whereas the acquired T cell-mediated protection against intracellular pathogens such as Leishmania major has been well studied in the past, the cells and mechanisms involved in their innate control are still poorly understood. Here, we investigated the role of natural killer T (NKT) cells in a high dose L. major mouse infection model. In vitro, L. major only weakly stimulated NKT cells and antagonized their response to the prototypic NKT cell ligand a-galactosylceramide, indicating that L. major partially escapes the activation of NKT cells. NKT cell deficiency as analyzed by subcutaneous infection of Ja281(-/-) mice (lacking invariant CD1d-restricted NKT cells) and CD1(-/-) mice (lacking all CD1d-restricted NKT cells) led to a transient increase in skin lesions, but did not impair the clinical cure of the infection, NK cell cytotoxicity, the production of IFN-gamma, the expression of inducible nitric oxide synthase, and the control of the parasites in the lymph node. In the spleen, however, NKT cells were required for NK cell cytotoxicity and early IFN-gamma production, they lowered the parasite burden, and exerted bystander effects on Leishmania antigen-specific T cell responses, most notably after systemic infection. Thus, NKT cells fulfill organ-specific protective functions during infection with L. major, but are not essential for parasite control. (c) 2005 Elsevier SAS. All rights reserved.