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用 Spp.(rSsEno)重组烯醇化酶免疫可有效预防小鼠孢子丝菌病。

Immunization with recombinant enolase of Sporothrix spp. (rSsEno) confers effective protection against sporotrichosis in mice.

机构信息

São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Clinical Analysis, Araraquara, SP, Brazil.

São Carlos Institute of Chemistry, University of São Paulo, São Carlos, SP, P.O. Box 780, 13560-970, Brazil.

出版信息

Sci Rep. 2019 Nov 20;9(1):17179. doi: 10.1038/s41598-019-53135-z.

Abstract

In recent years, research has focused on the immunoreactive components of the Sporothrix schenckii cell wall that can be relevant targets for preventive and therapeutic vaccines against sporotrichosis, an emergent worldwide mycosis. In a previous study, we identified a 47-kDa enolase as an immunodominant antigen in mice vaccinated with an adjuvanted mixture of S. schenckii cell wall proteins. Here, we sought to assess the protective potential of a Sporothrix spp. recombinant enolase (rSsEno) formulated with or without the adjuvant Montanide Pet-GelA (PGA) against the S. brasiliensis infection in mice. Mice that were immunized with rSsEno plus PGA showed increased antibody titters against rSsEno and increased median survival time when challenged with S. brasiliensis as compared with mice that had not been immunized or that were immunized with rSsEno alone. Immunization with rSsEno plus PGA induced a predominantly T-helper 1 cytokine pattern after in vitro stimulation of splenic cells with rSsEno: elevated levels of IFN-γ and IL-2, as well as of other cytokines involved in host defense against sporotrichosis, such as TNF-alpha, IL-6, and IL-4. Furthermore, we show for the first time the presence of enolase in the cell wall of both S. schenckii and S. brasiliensis. As a whole, our results suggest that enolase could be used as a potential antigenic target for vaccinal purposes against sporotrichosis.

摘要

近年来,研究集中在申克孢子丝菌细胞壁的免疫反应成分上,这些成分可能是预防和治疗孢子丝菌病(一种新兴的世界性真菌病)的疫苗的相关靶点。在之前的一项研究中,我们在用佐剂混合物(S. schenckii 细胞壁蛋白)接种的小鼠中鉴定出 47kDa 烯醇酶作为免疫优势抗原。在这里,我们试图评估 Sporothrix spp. 重组烯醇酶(rSsEno)与或不与佐剂 Montanide Pet-GelA(PGA)联合配方对巴西利昂孢子丝菌感染的保护潜力。与未免疫或单独用 rSsEno 免疫的小鼠相比,用 rSsEno 加 PGA 免疫的小鼠对 rSsEno 的抗体滴度增加,并且在受到巴西利昂孢子丝菌挑战时的中位存活时间增加。用 rSsEno 加 PGA 免疫诱导了脾细胞在体外用 rSsEno 刺激后的主要 T 辅助 1 细胞因子模式:IFN-γ和 IL-2 水平升高,以及其他参与宿主防御孢子丝菌病的细胞因子,如 TNF-α、IL-6 和 IL-4。此外,我们首次证明烯醇酶存在于申克孢子丝菌和巴西利昂孢子丝菌的细胞壁中。总的来说,我们的结果表明烯醇酶可以作为一种潜在的抗原靶点,用于预防孢子丝菌病的疫苗接种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e107/6868355/10e7168f0560/41598_2019_53135_Fig1_HTML.jpg

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