Trichinella spiralis paramyosin activates mouse bone marrow-derived dendritic cells and induces regulatory T cells.
Trichinella spiralis paramyosin activates mouse bone marrow-derived dendritic cells and induces regulatory T cells.
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DOI：
10.1186/s13071-016-1857-y
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发表时间：
2016-11-04
影响因子：
3.2
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Guo K;Sun X;Gu Y;Wang Z;Huang J;Zhu X
背景：树突状细胞（Dendritic cells，DCs）是一种抗原提呈细胞，在多种感染性疾病中调节T细胞应答。旋毛虫组织寄生线虫不仅表达副肌球蛋白（TsPmy）作为结构蛋白，而且作为免疫调节剂，通过结合一些宿主补体成分来减轻补体攻击。TsPmy是否参与其他免疫调节途径以及TsPmy如何与宿主DCs相互作用尚不清楚。通过表面标志物CD 40、CD 80、CD 86和MHCII的表达来确定DC的成熟。将rTsPmy致敏的DC与T.使用流式细胞术观察它们在T细胞上的活化和极化调节性T细胞。结果：TsPmy能激活小鼠骨髓来源的DC至半成熟状态，表达表面CD 40和CD 86，但不表达表面CD 80和MHCII。半成熟的TsPmy致敏的DC能够刺激T.螺旋体致敏的CD 4 +T细胞增殖。将TsPmy脉冲的DC与幼稚的CD 4+脾细胞孵育，使后者极化为CD 4 + CD 25 + Foxp 3+调节性T细胞。而rTsPmy免疫小鼠仅诱导产生CD 4 + CD 25-Foxp 3 +T细胞群，并伴有高水平的IL-10、TGF-β和IL-17 A。在感染旋毛虫后，TsPmy通过刺激DC将CD 4 +T细胞分化为调节性T细胞，除了与宿主补体级联的组分结合之外，作为在宿主中生存的生存策略，在调节宿主免疫系统中起重要作用。
Background:Dendritic cells (DCs) are antigen-presenting cells that regulate T cell responses for many infectious diseases. The tissue-dwelling nematode Trichinella spiralis expresses paramyosin (TsPmy) not only as a structural protein but also as an immunomodulator to alleviate complement attack by binding to some host complement components. Whether TsPmy is involved in other immunomodulatory pathway and how TsPmy interacts with host DCs is still unknown.Methods:Mouse bone marrow-derived DCs were incubated with recombinant TsPmy (rTsPmy) for activation. Maturation of DC was determined by the expression of surface markers CD40, CD80, CD86 and MHCII. The rTsPmy-pulsed DCs were co-incubated with T. spiralis-sensitized or naïve mouse CD4+T cells to observe their activation on T cells and polarizing regulatory T cells using flow cytometry. Cytokines were measured by enzyme-linked immunosorbent assays (ELISA).Results:TsPmy was able to activate mouse bone marrow-derived DCs to semi-mature status characterized by expressing surface CD40 and CD86, but not CD80 and MHCII. The semi-mature TsPmy-pulsed DCs were able to stimulate T. spiralis-sensitized CD4+T cells to proliferate. Incubation of TsPmy-pulsed DCs with naïve CD4+splenocytes polarized the latter to CD4+CD25+Foxp3+regulatory T cells. However, mice immunized with rTsPmy only induce the CD4+CD25-Foxp3+T cell population, associated with high level of IL-10, TGF-β and IL-17A.Conclusions:During T. spiralis infection, TsPmy plays an important role in modulating the host immune system by stimulating DCs to differentiate the CD4+T cells to regulatory T cells, in addition to binding to components of the host complement cascade, as survival strategies to live in host.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
5.4
作者：
Osorio, Fabiola;LeibundGut-Landmann, Salome;Lochner, Matthias;Lahl, Katharina;Sparwasser, Tim;Eberl, Gerard;Reis e Sousa, Caetano
通讯作者：
Reis e Sousa, Caetano
DOI：
10.1073/pnas.1510760112
发表时间：
2015-11-10
影响因子：
11.1
作者：
Hu, Wei;Jain, Aakanksha;Pasare, Chandrashekhar
通讯作者：
Pasare, Chandrashekhar
影响因子：
2.2
作者：
Aranzamendi, C.;Fransen, F.;Pinelli, E.
通讯作者：
Pinelli, E.