Trichinella spiralis Excretory-Secretory Products Stimulate Host Regulatory T Cell Differentiation through Activating Dendritic Cells
Trichinella spiralis Excretory-Secretory Products Stimulate Host Regulatory T Cell Differentiation through Activating Dendritic Cells
复制标题
旋毛虫排泄分泌产物通过激活树突状细胞刺激宿主调节性 T 细胞分化
DOI：
10.3390/cells8111404
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发表时间：
2019-11-01
期刊：
影响因子：
6
通讯作者：
Zhu, Xinping
中科院分区：
文献类型：
--
作者：
Sun, Xi-Meng;Guo, Kai;Zhu, Xinping
旋毛虫在宿主体内维持慢性感染，涉及多种免疫调节特性，其机制尚未完全阐明。在本研究中，我们发现T.旋毛虫感染通过寄生虫排泄分泌（ES）产物诱导强烈的调节性T细胞应答，其特征在于CD 4（+）CD 25（+）Foxp 3（+）和CD 4（+）CD 25（-）Foxp 3（+）Treg细胞增加，伴随高水平的IL-10和TGF-β。T.旋毛虫成虫排泄-分泌产物（AES）和肌幼虫排泄-分泌产物（MES）均能够在体外激活BMDC以促进其成熟并产生调节性细胞因子IL-10和TGF-β。霸王螺旋藻AES和MES致敏的树突状细胞（Dendritic cells，DC）不仅具有向致敏的CD 4（+）T细胞提呈抗原以刺激其增殖的能力，而且具有诱导幼稚CD 4（+）T细胞分化为分泌IL-10和TGF-β的Treg细胞的能力。T. spiralis AES和MES脉冲的骨髓来源的树突状细胞（BMDC）赋予幼稚小鼠获得Treg细胞的分化。T. spiralis AES具有比MES更好的诱导Treg细胞的能力，尽管后者具有诱导CD 4（+）CD 25（-）Foxp 3（+）Treg细胞的能力。本研究结果表明，T.旋毛虫ES产物可能通过激活树突状细胞来刺激宿主Treg细胞的分化，以创造有利于寄生虫在宿主中存活的调节环境。
Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory-secretory (ES) products, characterized by increase of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) Treg cells accompanied by high levels of IL-10 and TGF-beta. T. spiralis adult worm excretory-secretory products (AES) and muscle larvae excretory-secretory products (MES) were both able to activate BMDCs in vitro to facilitate their maturation and to create regulatory cytokines IL-10 and TGF-beta. The T. spiralis AES- and MES-pulsed dendritic cells (DCs) possessed abilities not only to present antigens to sensitized CD4(+) T cell to stimulate their proliferation but also to induce naive CD4(+) T cells to differentiate to Treg cells secreting IL-10 and TGF-beta. The passive transfer of T. spiralis AES- and MES-pulsed bone marrow-derived dendritic cells (BMDCs) conferred the naive mice to acquire the differentiation of Treg cells. T. spiralis AES possesses a better ability to induce Treg cells than did MES, although the latter has the ability to induce CD4(+)CD25(-)Foxp3(+) Treg cells. The results obtained in this study suggested that T. spiralis ES products stimulate the differentiation of host Treg cells possibly through activating dendritic cells to create a regulatory environment that benefits the survival of the parasite in the host.