Plasmacytoid dendritic cells are activated by Toxoplasma gondii to present antigen and produce cytokines

Plasmacytoid dendritic cells are activated by Toxoplasma gondii to present antigen and produce cytokines
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DOI:
10.4049/jimmunol.180.9.6229
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发表时间:
2008-05-01
影响因子:
4.4
通讯作者:
Hunter, Christopher A.
Hunter, Christopher A.
中科院分区:
医学2区
文献类型:
--
作者:
Pepper, Marion;Dzierszinski, Florence;Hunter, Christopher A.

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感染寄生虫弓形虫导致诱导的Th 1型反应占主导地位的IFN-γ的生产和控制这种病原体。先天免疫系统的细胞在通过产生IL-12以及将寄生虫衍生的Ag呈递给MHC限制性T细胞来启动这种应答中是必不可少的。虽然树突状细胞(DC)已被牵连在这些事件中,个别DC群体的贡献仍然不清楚。因此,多参数流式细胞术用于鉴定和表征急性弓形虫病期间小鼠DC的亚群。这种方法证实了感染导致常规DC(cDC)亚群的扩增和活化。然而,出乎意料的是,该分析进一步揭示了浆细胞样DC也被扩增,并且这些细胞上调与其获得的初始初始CD 4(+)T细胞的能力相关的MHC II类和共刺激分子。此外,T.刚地氏体激活的浆细胞样DC产生高水平的IL-12,并且浆细胞样DC成熟和细胞因子产生都依赖于TLR 11。总之,这些研究表明,pDC是参与T细胞增殖的初始阶段的重要DC亚群。弓形虫感染,呈递寄生虫Ag并产生对控制感染重要的细胞因子。
Infection with the parasite Toxoplasma gondii leads to the induction of a Th1-type response dominated by IFN-gamma production and control of this pathogen. Cells of the innate immune system are essential in initiating this response both through the production of IL-12 as well as the presentation of parasite-derived Ags to MHC-restricted T cells. Although dendritic cells (DCs) have been implicated in these events, the contribution of individual DC populations remains unclear. Therefore, multiparameter flow cytometry was used to identify and characterize subsets of murine DCs during acute toxoplasmosis. This approach confirmed that infection leads to the expansion and activation of conventional DC (cDC) subsets. Unexpectedly, however, this analysis further revealed that plasmacytoid DCs are also expanded and that these cells up-regulate MHC class II and costimulatory molecules associated with their acquired ability to prime naive CD4(+) T cells. Furthermore, T. gondii-activated plasmacytoid DCs produce high levels of IL-12 and both plasmacytoid DC maturation and cytokine production are dependent on TLR11. Together these studies suggest that pDCs are a prominent DC subset involved in the initial stages of T. gondii infection, presenting parasite Ags and producing cytokines that are important for controlling infection.