Vibrio vulnificus infection induces the maturation and activation of dendritic cells with inflammatory Th17-polarizing ability
Vibrio vulnificus infection induces the maturation and activation of dendritic cells with inflammatory Th17-polarizing ability
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DOI：
10.3892/ijmm.2017.3230
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发表时间：
2018-01-01
影响因子：
5.4
通讯作者：
Kim, Tae Sung
中科院分区：
文献类型：
--
作者：
Lee, Arim;Lim, Hui Xuan;Kim, Tae Sung
创伤弧菌是一种革兰氏阴性细菌，通过食用受污染的海鲜或伤口感染引起危及生命的败血症和胃肠炎。此外，创伤弧菌感染可刺激多种致炎细胞因子的产生，这些细胞因子与主要由树突状细胞(DC)介导的炎症反应有关，树突状细胞(DC)起抗原递呈细胞的作用。本研究旨在探讨创伤弧菌感染是否诱导具有极化T辅助(Th)细胞为Th17细胞能力的小鼠树突状细胞的成熟和激活。已知调节失调的Th17细胞反应会导致组织损伤，促进病原体的渗透；然而，Th17细胞也参与宿主对感染的防御。创伤弧菌感染后，CD40、CD80和主要组织相容性复合体II类等细胞表面分子的表达显著增加，导致DC成熟和活化。在本研究中，通过对创伤弧菌感染DC的细胞因子谱的分析，发现创伤弧菌感染的DC优先产生IL-1和IL-6，通过IL-1和IL-6诱导初始的CD4(+)T细胞共同孵育时Th17细胞的极化。通过使用抗IL-6中和抗体减少Th17细胞的产生，表明创伤弧菌的Th17极化能力主要依赖于DC来源的IL-6。创伤弧菌感染的树突状细胞在体内持续增加小鼠淋巴结中的Th17细胞数量。最后，小鼠口服创伤弧菌也增加了小肠固有层的Th17细胞反应。这些结果共同证明创伤弧菌通过树突状细胞诱导Th17细胞炎症反应，这可能与创伤弧菌感染引起的免疫病理效应有关。
Vibrio vulnificus (V. vulnificus) is a gram-negative bacterium, which causes life-threatening septicemia and gastroenteritis through the consumption of contaminated seafood or wound infection. In addition, V. vulnificus infection is known to stimulate the production of several pro-inflammatory cytokines, which are associated with inflammatory responses mediated predominantly by dendritic cells (DCs), functioning as antigen-presenting cells. The present study aimed to investigate whether V. vulnificus infection induced the maturation and activation of murine DCs, which have the ability to polarize T helper (Th) cells into Th17 cells. Dysregulated Th17 cell responses are known to cause tissue damage, promoting the penetration of pathogens; however, Th17 cells are also involved in host defense against infection. Infection with V. vulnificus significantly increased the expression of cell surface molecules, including CD40, CD80 and major histocompatibility complex class II, leading to the maturation and activation of DCs. In the present study, the analysis of the cytokine profiles of DCs upon infection with V. vulnificus revealed the preferential production of interleukin-1 (IL-1) and IL-6, through which V. vulnificus-infected DCs induced the polarization of Th17 cells when naive CD4(+) T cells were co-incubated. The reduction of Th17 cell generation through the use of anti-IL-6 neutralizing antibodies indicated that the Th17-polarizing capacity of V. vulnificus was predominantly dependent on DC-derived IL-6. The in vivo administration of V. vulnificus-infected DCs consistently increased the Th17 cell population in the lymph nodes of mice. Finally, the oral administration of V. vulnificus in mice also increased Th17 cell responses in the lamina propria of the small intestine. These results collectively demonstrated that V. vulnificus induced inflammatory Th17 cell responses via DCs, which may be associated with the immunopathological effects caused by V. vulnificus infection.