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首页> 外文期刊>Infection and immunity >A Live and Inactivated Chlamydia trachomatis Mouse Pneumonitis Strain Induces the Maturation of Dendritic Cells That Are Phenotypically and Immunologically Distinct
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A Live and Inactivated Chlamydia trachomatis Mouse Pneumonitis Strain Induces the Maturation of Dendritic Cells That Are Phenotypically and Immunologically Distinct

机译:活的和灭活的沙眼衣原体小鼠肺炎株诱导表型和免疫学上不同的树突状细胞的成熟。

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The intracellular bacterial pathogen Chlamydia trachomatis is a major cause of sexually transmitted disease worldwide. While protective immunity does appear to develop following natural chlamydial infection in humans, early vaccine trials using heat-killed C. trachomatis resulted in limited and transient protection with possible enhanced disease during follow-up. Thus, immunity following natural infection with live chlamydia may differ from immune responses induced by immunization with inactivated chlamydia. To study this differing immunology, we used murine bone marrow-derived dendritic cells (DC) to examine DC maturation and immune effector function induced by live and UV-irradiated C. trachomatis elementary bodies (live EBs and UV-EB, respectively). DC exposed to live EBs acquired a mature DC morphology; expressed high levels of major histocompatibility complex (MHC) class II, CD80, CD86, CD40, and ICAM-1; produced elevated amounts of interleukin-12 and tumor necrosis factor alpha; and were efficiently recognized by Chlamydia-specific CD4+ T cells. In contrast, UV-EB-pulsed DC expressed low levels of CD40 and CD86 but displayed high levels of MHC class II, ICAM-1, and CD80; secreted low levels of proinflammatory cytokines; and exhibited reduced recognition by Chlamydia-specific CD4+ T cells. Adoptive transfer of live EB-pulsed DC was more effective than that of UV-EB-pulsed DC at protecting mice against challenge with live C. trachomatis. The expression of DC maturation markers and immune protection induced by UV-EB could be significantly enhanced by costimulation of DC ex vivo with UV-EB and oligodeoxynucleotides containing cytosine phosphate guanosine; however, the level of protection was significantly less than that achieved by using DC pulsed ex vivo with viable EBs. Thus, exposure of DC to live EBs results in a mature DC phenotype which is able to promote protective immunity, while exposure to UV-EB generates a semimature DC phenotype with less protective potential. This result may explain in part the differences in protective immunity induced by natural infection and immunization with whole inactivated organisms and is relevant to rational chlamydia vaccine design strategies.
机译:细胞内细菌病原体沙眼衣原体是全世界性传播疾病的主要原因。虽然人类天然衣原体感染后似乎确实会产生保护性免疫,但使用热灭活的 C进行早期疫苗试验。沙眼炎导致随访过程中有限的暂时性保护,可能会加重疾病。因此,自然感染活衣原体感染后的免疫力可能不同于灭活衣原体免疫所诱导的免疫反应。为了研究这种不同的免疫学,我们使用了鼠骨髓来源的树突状细胞(DC)来研究活的和紫外线照射的 C诱导的DC成熟和免疫效应功能。沙眼基本体(分别是活的EB和UV-EB)。暴露于活的EB的DC具有成熟的DC形态;表达高水平的II类主要组织相容性复合物(MHC),CD80,CD86,CD40和ICAM-1;产生升高量的白介素12和肿瘤坏死因子α;并被衣原体特异的CD4 + T细胞有效识别。相反,UV-EB脉冲的DC表达低水平的CD40和CD86,但显示高水平的II类MHC,ICAM-1和CD80。分泌低水平的促炎细胞因子;并显示出衣原体特异性CD4 + T细胞的识别能力下降。活的EB脉冲DC的过继转移在保护小鼠免受活的C挑战方面比UV-EB的DC更有效。沙眼。通过体外共刺激UV-EB和含有胞嘧啶磷酸鸟苷的寡聚脱氧核苷酸可以显着增强UV-EB诱导的DC成熟标志物的表达和免疫保护。但是,其保护水平明显低于使用活体外EB的DC脉冲体外获得的水平。因此,将DC暴露于活的EB会产生成熟的DC表型,能够促进保护性免疫,而暴露于UV-EB会产生具有较小保护电位的半成熟DC表型。该结果可以部分解释自然感染和整个灭活生物体免疫诱导的保护性免疫的差异,并且与合理的衣原体疫苗设计策略有关。

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