Intracellular Salmonella inhibit antigen presentation by dendritic cells
Intracellular Salmonella inhibit antigen presentation by dendritic cells
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DOI：
10.4049/jimmunol.174.5.2892
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Hensel, M
中科院分区：
文献类型：
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作者：
Cheminay, C;Möhlenbrink, A;Hensel, M
树突状细胞（DC）是连接固有免疫和适应性免疫的重要抗原提呈细胞。在对树突状细胞内肠炎沙门氏菌的细胞内活动进行分析时，我们观察到活菌抑制抗原依赖性T细胞增殖。这种效应依赖于树突状细胞诱导型一氧化氮合酶的诱导以及沙门氏菌致病岛2（SPI2）中毒力基因的功能。沙门氏菌的细胞内活动不影响树突状细胞的活力、抗原摄取或成熟，但导致MHC II类分子对抗原肽的呈递减少。与接种SPI2完整沙门氏菌的小鼠相比，接种SPI2缺陷型沙门氏菌的小鼠在再次感染时抵抗力增强，这与CD4⁺以及CD8⁺T细胞数量增加相关。我们的研究是细胞内细菌病原体干扰树突状细胞抗原呈递的首个实例。树突状细胞功能的颠覆是这种病原体为逃避免疫防御、在宿主器官定植并在感染宿主中持续存在而采用的一种新策略。
Dendritic cells (DC) are important APCs linking innate and adaptive immunity. During analysis of the intracellular activities of Salmonella enterica in DC, we observed that viable bacteria suppress Ag-dependent T cell proliferation. This effect was dependent on the induction of inducible NO synthase by DC and on the function of virulence genes in Salmonella pathogenicity island 2 (SPI2). Intracellular activities of Salmonella did not affect the viability, Ag uptake, or maturation of DC, but resulted in reduced presentation of antigenic peptides by MHC class 11 molecules. Increased resistance to reinfection was observed after vaccination of mice with SPI2-deficient Salmonella compared with mice vaccinated with SPI2-proficient Salmonella, and this correlated with an increased amount of CD4(+) as well as CD8(+) T cells. Our study is the first example of interference of an intracellular bacterial pathogen with Ag presentation by DC. The subversion of DC functions is a novel strategy deployed by this pathogen to escape immune defense, colonize host organs, and persist in the infected host.