Bordetella pertussis-infected human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization and interleukin-23 expression
Bordetella pertussis-infected human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization and interleukin-23 expression
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DOI：
10.1128/iai.73.3.1590-1597.2005
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发表时间：
2005-03-01
影响因子：
3.1
通讯作者：
Ausiello, CM
中科院分区：
文献类型：
--
作者：
Fedele, G;Stefanelli, P;Ausiello, CM
百日咳博德特氏菌是百日咳的病原体，可被多种细胞类型内化，包括上皮细胞、单核细胞和中性粒细胞。尽管其在细胞内存活的能力仍存在争议，但已证明细胞介导的免疫（CMI）在保护中起着关键作用。在本研究中，我们旨在阐明百日咳博德特氏菌与人单核细胞衍生的树突状细胞（MDDC）的相互作用，评估该细菌进入MDDC、在细胞内存活、干扰成熟过程和功能活动以及影响宿主免疫反应的能力。所获得的结果表明，百日咳博德特氏菌被MDDC内化以及在MDDC内存活的能力较低。在与细菌接触后，未成熟的MDDC被诱导发生表型成熟并获得抗原呈递细胞功能。尽管百日咳博德特氏菌诱导产生高水平的白细胞介素 - 10（IL - 10）以及几乎检测不到水平的IL - 12，但该细菌诱导了MDDC和辅助性T细胞1（Th1）极化效应细胞的成熟。对IL - 12细胞因子家族的基因表达分析清楚地表明，百日咳博德特氏菌诱导产生高水平的IL - 23的p40和p19亚单位，但未能诱导IL - 12的p35亚单位的表达。总体而言，我们的研究结果表明，百日咳博德特氏菌即使仅在MDDC中短暂存活，也会促进IL - 23（一种新发现的Th1极化细胞因子）的合成。因此允许产生Th1导向的免疫反应，这与诱导适当的CMI反应相关，并且是自然感染或全细胞疫苗接种所诱导的保护的典型特征。
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.