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树突状细胞能够特异性识别申克孢子丝菌抗原,并在体外促进 Th1/Th17 反应。

Dendritic cell are able to differentially recognize Sporothrix schenckii antigens and promote Th1/Th17 response in vitro.

机构信息

Department of Clinical Analyses, Faculty of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo 14801-902, Brazil.

出版信息

Immunobiology. 2012 Aug;217(8):788-94. doi: 10.1016/j.imbio.2012.04.006. Epub 2012 May 9.

Abstract

Sporotrichosis is a disease caused by the dimorphic fungus Sporothrix schenckii. The main clinical manifestations occur in the skin, however the number of systemic and visceral cases has increased, especially in immunocompromised patients. Dendritic cells (DCs) are highly capable to recognize the fungus associated data and translate it into differential T cells responses both in vivo and in vitro. Although, the mechanisms involved in the interaction between DCs and S. schenckii are not fully elucidated. The present study investigated the phenotypic and functional changes in bone marrow dendritic cells (BMDCs) stimulated in vitro with the yeast form of S. schenckii or exoantigen (ExoAg) and its ability to trigger a cellular immune response in vitro. Our results demonstrated that the live yeast of S. schenckii and its exoantigen, at a higher dose, were able to activate BMDCs and made them capable of triggering T cell responses in vitro. Whereas the yeast group promoted more pronounced IFN-γ production rather than IL-17, the Exo100 group generated similar production of both cytokines. The exoantigen stimulus suggests a capability to deviate the immune response from an effector Th1 to an inflammatory Th17 response. Interestingly, only the Exo100 group promoted the production of IL-6 and a significant increase of TGF-β, in addition to IL-23 production. Interestingly, only Exo100 group was capable to promote the production of IL-6 and a significant increase on TGF-β, in addition with IL-23 detection. Our results demonstrated the plasticity of DCs in translating the data associated with the fungus S. schenckii and ExoAg into differential T cell responses in vitro. The possibility of using ex vivo-generated DCs as vaccinal and therapeutic tools for sporotrichosis is a challenge for the future.

摘要

申克孢子丝菌病是一种由双相真菌申克孢子丝菌引起的疾病。主要的临床表现发生在皮肤,但系统性和内脏病例的数量有所增加,尤其是在免疫功能低下的患者中。树突状细胞(DC)具有高度识别与真菌相关数据的能力,并在体内和体外将其转化为不同的 T 细胞反应。然而,DC 与 S.schenckii 相互作用的机制尚未完全阐明。本研究探讨了体外用 S.schenckii 酵母形式或外抗原(ExoAg)刺激骨髓树突状细胞(BMDC)后其表型和功能的变化,以及其在体外触发细胞免疫反应的能力。我们的结果表明,活酵母形式的 S.schenckii 及其外抗原,在较高剂量下,能够激活 BMDCs,并使其能够在体外触发 T 细胞反应。虽然酵母组促进了更多 IFN-γ的产生,而不是 IL-17,但 Exo100 组产生了两种细胞因子的相似产量。外抗原刺激提示其具有将免疫反应从效应性 Th1 偏向炎症性 Th17 反应的能力。有趣的是,只有 Exo100 组促进了 IL-6 的产生,并显著增加了 TGF-β的产生,此外还检测到了 IL-23 的产生。有趣的是,只有 Exo100 组能够促进 IL-6 的产生,并显著增加 TGF-β的产生,此外还检测到了 IL-23 的产生。我们的结果表明,DC 具有将与 S.schenckii 真菌和 ExoAg 相关的数据转化为体外不同 T 细胞反应的可塑性。利用体外生成的 DC 作为孢子丝菌病疫苗和治疗工具的可能性是未来的挑战。

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