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首页> 外文期刊>Infection and immunity >Burkholderia pseudomallei Proteins Presented by Monocyte-Derived Dendritic Cells Stimulate Human Memory T Cells In Vitro
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Burkholderia pseudomallei Proteins Presented by Monocyte-Derived Dendritic Cells Stimulate Human Memory T Cells In Vitro

机译：单核细胞衍生的树突状细胞呈现的伯克霍尔德菌假mallei蛋白体外刺激人类记忆T细胞。

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Melioidosis is a severe infectious disease caused by the saprophytic facultative intracellular pathogen Burkholderia pseudomallei. The disease is endemic in Southeast Asia and Northern Australia, and no effective vaccine exists. To describe human cell-mediated immune responses to B. pseudomallei and to identify candidate antigens for vaccine development, the ability of antigen-pulsed monocyte-derived dendritic cells (moDCs) to trigger autologous T-cell responses to B. pseudomallei and its products was tested. moDCs were prepared from healthy individuals exposed or not exposed to B. pseudomallei, based on serological evidence. These were pulsed with heat-killed B. pseudomallei or purified antigens, including ABC transporters (LolC, OppA, and PotF), Bsa type III secreted proteins (BipD and BopE), tandem repeat sequence-containing proteins (Rp1 and Rp2), flagellin, and heat shock proteins (Hsp60 and Hsp70), prior to being mixed with autologous T-cell populations. After pulsing of cells with either heat-killed B. pseudomallei, LolC, or Rp2, coculturing the antigen-pulsed moDCs with T cells elicited gamma interferon production from CD4+ T cells from seropositive donors at levels greater than those for seronegative donors. These antigens also induced granzyme B (cytotoxic) responses from CD8+ T cells. Activation of antigen-specific CD4+ T cells required direct contact with moDCs and was therefore not dependent on soluble mediators. Rp peptide epitopes recognized by T cells in healthy individuals were identified. Our study provides valuable novel data on the induction of human cell-mediated immune responses to B. pseudomallei and its protein antigens that may be exploited in the rational development of vaccines to combat melioidosis.
机译：类胡oid病是由腐生性兼性细胞内病原体 Burkholderia pseudomallei 引起的严重传染病。该病在东南亚和北澳大利亚是地方病，不存在有效的疫苗。描述人类细胞介导的对B的免疫反应。假单胞菌并鉴定用于疫苗开发的候选抗原，即抗原脉冲单核细胞衍生的树突状细胞（moDC）触发自体T细胞对 B的反应的能力。测试了假苹果酱及其产品。 moDC由暴露于或未暴露于B的健康个体制备。基于血清学证据的假小麦芽。将它们用热灭活的B脉冲。假Mallei 或纯化的抗原，包括ABC转运蛋白（LolC，OppA和PotF），Bsa III型分泌蛋白（BipD和BopE），​​含有串联重复序列的蛋白（Rp1和Rp2），鞭毛蛋白和热激蛋白（Hsp60和Hsp70），然后与自体T细胞群体混合。用任一种热灭活的 B脉冲细胞后。伪小分子，LolC或Rp2，将抗原脉冲的moDC与T细胞共培养，会从血清阳性患者的CD4 + T细胞中产生γ干扰素，其水平要高于血清阴性患者。这些抗原还诱导了CD8 + T细胞的颗粒酶B（细胞毒性）反应。抗原特异性CD4 + T细胞的激活需要直接与moDCs接触，因此不依赖于可溶性介体。鉴定了健康个体中T细胞识别的Rp肽表位。我们的研究提供了有关人类细胞介导的对B免疫应答的有价值的新颖数据。假疟原虫及其蛋白抗原可用于合理开发抗类流感的疫苗。

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