Immunogenicity and protective effect of recombinant enolase of Candida albicans in a murine model of systemic candidiasis
Immunogenicity and protective effect of recombinant enolase of Candida albicans in a murine model of systemic candidiasis
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DOI：
10.1080/13693780310001644653
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发表时间：
2004-08-01
期刊：
影响因子：
2.9
通讯作者：
La Valle, R
中科院分区：
文献类型：
--
作者：
Montagnoli, C;Sandini, S;La Valle, R
烯醇化酶是一种46 kda糖酵解酶，是条件致病菌白色念珠菌的免疫优势抗原。重组6 x his标记烯醇化酶与白细胞介素-12 （IL-12）联合研究，在小鼠血源性念珠菌病模型中作为细胞因子诱导的辅助剂。与未免疫或IL-12处理的小鼠相比，用烯醇化酶和IL-12免疫的小鼠显示出针对烯醇化酶的抗体滴度增加，中位生存时间延长，肾脏真菌负荷减少。这种增加的存活率可归因于烯醇化酶诱导的细胞介导免疫，因为它也发生在b细胞缺陷小鼠中。烯醇化酶免疫刺激脾细胞中主要的T-辅助性1 （Thl）细胞因子模式，并诱导纯化的CD4(+) T细胞产生干扰素- γ (ifn - γ)和白细胞介素-2 （IL-2）。然而，尽管免疫原性提高，重组烯醇化酶仅诱导了对播散性念珠菌病的适度保护，表明一种可能归因于诱导Thl细胞介导的免疫反应的保护形式。
Enolase, a 46-kDa glycolytic enzyme, is an immunodominant antigen of the opportunistic pathogen Candida albicans. A recombinant 6 x His-tagged enolase was studied, in conjunction with interleukin-12 (IL-12), as an adjuvant for cytokine induction favouring protection in a murine model of haematogenous candidiasis. Mice immunized with enolase plus IL-12 showed increased antibody titres against enolase, as well as increased median survival time and decreased fungal burden in kidneys, in comparison to non-immunized or IL-12-treated mice. This increased survival was attributable to enolase-induced cell-mediated immunity as it also occurred in B-cell-deficient mice. Enolase immunization stimulated a predominant T-helper-1 (Thl) cytokine pattern in splenic cells and induced production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by purified CD4(+) T cells. However, despite the elevation of immunogenicity, recombinant enolase induced only a modest protection against disseminated candidiasis, suggesting a form of protection likely attributable to the induction of a Thl cell-mediated immune response.