Vibrio cholerae ghosts (VCG) exert immunomodulatory effect on dendritic cells for enhanced antigen presentation and induction of protective immunity.
Vibrio cholerae ghosts (VCG) exert immunomodulatory effect on dendritic cells for enhanced antigen presentation and induction of protective immunity.
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Vibrio Cholerae Ghosts（VCG）对树突状细胞发挥免疫调节作用，以增强抗原表现和诱导保护性免疫。
DOI：
10.1186/s12865-014-0056-x
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发表时间：
2014-12-31
期刊：
影响因子：
3
通讯作者：
Igietseme JU
中科院分区：
文献类型：
--
作者：
Eko FO;Mania-Pramanik J;Pais R;Pan Q;Okenu DM;Johnson A;Ibegbu C;He C;He Q;Russell R;Black CM;Igietseme JU
我们先前表明，霍乱弧菌血影平台（VCG;空霍乱弧菌细胞包膜）是一种有效的疫苗抗原递送系统，可在不存在外部佐剂的情况下促进诱导实质性免疫。然而，这些细胞包膜增强免疫力和刺激主要是Th 1细胞和体液免疫应答的机制尚未阐明。我们假设VCG的免疫刺激能力涉及树突状细胞（DC）活化。本研究的目的是：a）研究DC [使用小鼠骨髓来源的DC（BMDCs）作为模型系统]摄取和内化VCGs的能力; B）评价内化的VCGs对DC活化和成熟的免疫调节作用及其向初始和感染致敏的CD 4 + T细胞呈递衣原体抗原的功能能力; c）评估VCG增强衣原体抗原的保护性免疫的能力。VCG被DC有效地内化而不影响其活力并调节DC介导的免疫应答。VCG脉冲的DC表现出增加的促炎细胞因子的分泌和与DC成熟相关的共刺激分子的表达，以响应UV照射的衣原体基本体（UV-EBs）的刺激。此外，这种相互作用导致有效的衣原体抗原呈递给感染致敏的但不是幼稚的CD 4 + T细胞，并增强保护性免疫。本研究表明，VCG激活DC，导致与DC激活和成熟相关的共刺激分子的表面表达，并增强衣原体抗原诱导的保护性免疫。结果表明，VCG的免疫增强活性增加T细胞活化抗原介导的，至少部分，通过DC触发。因此，VCG可以作为免疫调节剂，将抗原靶向DC，以增强针对微生物感染的保护性免疫。
We previously showed that the Vibrio cholerae ghost platform (VCG; empty V. cholerae cell envelopes) is an effective delivery system for vaccine antigens promoting the induction of substantial immunity in the absence of external adjuvants. However, the mechanism by which these cell envelopes enhance immunity and stimulate a predominantly Th1 cellular and humoral immune response has not been elucidated. We hypothesized that the immunostimulatory ability of VCG involves dendritic cell (DC) activation. The aims of this study were: a) to investigate the ability of DCs [using mouse bone marrow-derived DCs (BMDCs) as a model system] to take up and internalize VCGs; b) to evaluate the immunomodulatory effect of internalized VCGs on DC activation and maturation and their functional capacity to present chlamydial antigen to naïve and infection-sensitized CD4+ T cells and; c) to evaluate the ability of VCGs to enhance the protective immunity of a chlamydial antigen. VCGs were efficiently internalized by DCs without affecting their viability and modulated DC-mediated immune responses. VCG-pulsed DCs showed increased secretion of proinflammatory cytokines and expression of co-stimulatory molecules associated with DC maturation in response to stimulation with UV-irradiated chlamydial elementary bodies (UV-EBs). Furthermore, this interaction resulted in effective chlamydial antigen presentation to infection-sensitized but not naïve CD4+ T cells and enhancement of protective immunity. The present study demonstrated that VCGs activate DCs leading to the surface expression of co-stimulatory molecules associated with DC activation and maturation and enhancement of protective immunity induced by a chlamydial antigen. The results indicate that the immunoenhancing activity of VCG for increased T-cell activation against antigens is mediated, at least in part, through DC triggering. Thus, VCGs could be harnessed as immunomodulators to target antigens to DCs for enhancement of protective immunity against microbial infections.