Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice
Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice
复制标题
立克次体表面蛋白 Adr2 在 C3H/HeN 小鼠中诱导针对落基山斑疹热的保护性免疫。
DOI：
10.1016/j.vaccine.2014.02.057
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发表时间：
2014-04-11
期刊：
影响因子：
5.5
通讯作者：
Wen, Bohai
中科院分区：
文献类型：
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作者：
Gong, Wenping;Xiong, Xiaolu;Wen, Bohai
背景：立克次体是落基山斑疹热 (RMSF) 的病原体，这是一种危及生命的蜱传播感染。 Adr2是立克次体表面暴露的粘附蛋白，并在小鼠中研究其对RMSF的免疫保护作用。方法：用重组Adr2（rAdr2）免疫C3H/HeN小鼠，用立克次体攻击后检测小鼠各器官中的立克次体负荷。测定免疫小鼠血清中特异性抗体的水平，并将免疫小鼠血清用于中和立克次体。还检测了rAdr2刺激后立克次体感染小鼠分离的CD4(+)和CD8(+) T细胞的增殖和细胞因子分泌。结果：与阴性对照小鼠相比，立克次体攻击后，rAdr2免疫小鼠的脾、肝和肺中的立克次体负荷明显降低，这些器官的损伤程度明显较轻。 rAdr2免疫小鼠特异性IgG2a/IgG1的比例在免疫过程中不断增加。用rAdr2免疫血清处理后，粘附和侵入宿主细胞的立氏立克次体微生物总数显着低于用PBS免疫血清处理的数量。 rAdr2刺激后，立克次体感染小鼠CD4(+)或CD8(+) T细胞分泌的干扰素-γ和CD4(+) T细胞分泌的肿瘤坏死因子-α分别显着高于未感染小鼠。结论：Adr2是立克次体的保护性抗原。 Adr2提供的保护主要依赖于抗原特异性细胞介导的免疫反应，包括CD4(+)和CD8(+) T细胞的有效活性，产生大量TNF-α和/或IFN-γ以及特异性IgG2a的快速增加，协同激活和调理宿主细胞以杀死细胞内立克次体。 (C) 2014 Elsevier Ltd. 保留所有权利。
Background: Rickettsia rickettsii is the pathogen of Rocky Mountain spotted fever (RMSF), a life-threatening tick-transmitted infection. Adr2 was a surface-exposed adhesion protein of R. rickettsii and its immuno-protection against RMSF was investigated in mice.Methods: Recombinant Adr2 (rAdr2) was used to immunize C3H/HeN mice, and the rickettsial loads in organs of the mice were detected after challenge with R. rickettsii. The levels of specific antibodies of sera from the immunized mice were determined and the sera from immunized mice were applied to neutralize R. rickettsii. Proliferation and cytokine secretion of CD4(+) and CD8(+) T cells isolated from R. rickettsii-infected mice were also assayed after rAdr2 stimulation.Results: After R. rickettsii challenge, the rickettsial loads in spleens, livers, and lungs were significantly lower and the impairment degrees of these organs in rAdr2-immunized mice were markedly slighter, compared with those in negative control mice. The ratio of specific IgG2a/IgG1 of rAdr2-immunized mice kept increasing during the immunization. After treatment with rAdr2-immunized sera, the total number of R. rickettsii organisms adhering and invading host cells was significantly lower than that treated with PBS-immunized sera. Interferon-gamma secretion by CD4(+) or CD8(+) T cells and tumor necrosis factor-alpha secretion by CD4(+) T cells from R. rickettsii-infected mice were respectively significantly greater than those from uninfected mice after rAdr2 stimulation.Conclusion: Adr2 is a protective antigen of R. rickettsii. Protection offered by Adr2 is mainly dependent on antigen-specific cell-mediated immune responses, including efficient activity of CD4(+) and CD8(+) T cells to produce great amount of TNF-alpha and/or IFN-gamma as well as rapid increase of specific IgG2a, which synergistically activate and opsonize host cells to killing intracellular rickettsiae. (C) 2014 Elsevier Ltd. All rights reserved.