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首页> 外文期刊>Infection and immunity >Bordetella pertussis-Infected Human Monocyte-Derived Dendritic Cells Undergo Maturation and Induce Th1 Polarization and Interleukin-23 Expression
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Bordetella pertussis-Infected Human Monocyte-Derived Dendritic Cells Undergo Maturation and Induce Th1 Polarization and Interleukin-23 Expression

机译:百日咳博德特氏菌感染的人单核细胞衍生的树突状细胞成熟并诱导Th1极化和白介素23表达。

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Bordetella pertussis, the causative agent of whooping cough, is internalized by several cell types, including epithelial cells, monocytes, and neutrophils. Although its ability to survive intracellularly is still debated, it has been proven that cell-mediated immunity (CMI) plays a pivotal role in protection. In this study we aimed to clarify the interaction of B. pertussis with human monocyte-derived dendritic cells (MDDC), evaluating the ability of the bacterium to enter MDDC, to survive intracellularly, to interfere with the maturation process and functional activities, and to influence the host immune responses. The results obtained showed that B. pertussis had a low capability to be internalized by—and to survive in—MDDC. Upon contact with the bacteria, immature MDDC were induced to undergo phenotypic maturation and acquired antigen-presenting-cell functions. Despite the high levels of interleukin-10 (IL-10) and the barely detectable levels of IL-12 induced by B. pertussis, the bacterium induced maturation of MDDC and T helper 1 (Th1) polarized effector cells. Gene expression analysis of the IL-12 cytokine family clearly demonstrated that B. pertussis induced high levels of the p40 and p19 subunits of IL-23 yet failed to induce the expression of the p35 subunit of IL-12. Overall our findings show that B. pertussis, even if it survives only briefly in MDDC, promotes the synthesis of IL-23, a newly discovered Th1 polarizing cytokine. A Th1-oriented immune response is thus allowed, relevant in the induction of an adequate CMI response, and typical of protection induced by natural infection or vaccination with whole-cell vaccines.
机译:百日咳百日咳杆菌是由多种细胞类型内在化的,包括上皮细胞,单核细胞和中性粒细胞。尽管其在细胞内生存的能力仍在争论中,但已证明细胞介导的免疫(CMI)在保护中起着关键作用。在这项研究中,我们旨在阐明 B的相互作用。百日咳与人单核细胞衍生的树突状细胞(MDDC)一起评估细菌进入MDDC,在细胞内存活,干扰成熟过程和功能活性以及影响宿主免疫反应的能力。获得的结果显示为 B。百日咳不能被MDDC内化并在其中存活。与细菌接触后,未成熟的MDDC被诱导经历表型成熟并获得抗原呈递细胞功能。尽管白细胞介素10(IL-10)含量高,而 B诱导的IL-12含量却几乎检测不到。百日咳,该细菌诱导了MDDC和T辅助1(Th1)极化效应细胞的成熟。 IL-12细胞因子家族的基因表达分析清楚地证明了 B。百日咳诱导高水平的IL-23 p40和p19亚基,但未能诱导IL-12 p35亚基的表达。总的来说,我们的发现表明 B。百日咳即使在MDDC中仅能短暂存活,也会促进IL-23(一种新发现的Th1极化细胞因子)的合成。因此,允许以Th1为导向的免疫应答,与诱导适当的CMI应答有关,并且是自然感染或全细胞疫苗接种诱导的典型保护作用。

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