A 70-kilodalton recombinant heat shock protein of Candida albicans is highly immunogenic and enhances systemic murine candidiasis
A 70-kilodalton recombinant heat shock protein of Candida albicans is highly immunogenic and enhances systemic murine candidiasis
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DOI：
10.1128/iai.66.5.2154-2162.1998
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发表时间：
1998-05-01
影响因子：
3.1
通讯作者：
Cassone, A
中科院分区：
文献类型：
--
作者：
Bromuro, C;La Valle, R;Cassone, A
70-kDa重组白念珠菌热休克蛋白（CaHsp 70）及其21-kDa C端和28-kDa N端片段（分别为CaHsp 70-Cter和CaHsp 70-Nter）的免疫原性，包括体外和体内的促炎细胞因子诱导，以及在血源性念珠菌病小鼠模型中的保护作用，完整蛋白及其ma片段是小鼠抗体（Ab;免疫球蛋白G1 [IgG 1]和IgG 2b是流行同种型）和细胞介导免疫（CMI）应答的强诱导剂。CaHsp 70制剂也被健康人外周血单个核细胞识别为CMI靶点，CaHsp 70制剂接种于免疫小鼠诱导快速产生白细胞介素-6（IL-6）和肿瘤坏死因子α（TNF-α），在2 ~ 5 h达到峰值，24 h内下降，CaHsp 70和CaHsp 70-Cter也诱导γ干扰素（IFN-γ）产生（IFN-γ）、IL-12和IL-10，但不产生IL-4。特别地，IFN-γ的产生即使不上级也等于由完整的热灭活的真菌细胞或促有丝分裂凝集素伴刀豆球蛋白A在相同细胞中诱导的IFN-γ的产生。然而，在免疫小鼠中，在用CaHsp 70和CaHsp 70-Cter体外刺激CD 4（+）细胞时，除了IFN-γ之外，还产生IL-4而不是IL-12，与未免疫的小鼠相比，这些动物显示出减少的中位存活时间，并且它们的死亡率与真菌菌丝的器官侵入严格相关。它们的增强的易感性归因于免疫状态，因为它不发生在先天性无胸腺裸鼠中，其不能引起对CaHsp 70制剂的Ab或CMI应答。总之，我们的数据表明CaHsp 70的免疫原性升高，然而，在所使用的小鼠模型中似乎没有保护作用，而是对念珠菌感染有一定的增强作用。
The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immmnogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis, The whole protein and its ma fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects, Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h, CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-gamma), IL-12, and IL-10 but not IL-4 production by CD4(+) lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-gamma was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A, In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-gamma upon in vitro stimulation of CD4(+) cells with CaHsp70 and CaHsp70-Cter, These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae, Their enhanced susceptibility was attributable io the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise tither Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.