当前位置: X-MOL 学术J. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Targeting Antigens to Different Receptors on Conventional Type 1 Dendritic Cells Impacts the Immune Response
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-26 , DOI: 10.4049/jimmunol.1901119
Even Fossum 1 , Demo Yemane Tesfaye 2 , Sonja Bobic 2 , Arnar Gudjonsson 2 , Ranveig Braathen 2 , Mireille H Lahoud 3 , Irina Caminschi 3, 4 , Bjarne Bogen 1
Affiliation  

Key Points Targeting different receptors on cDC1s impacts immune responses. Targeting Xcr1 induces Th1 polarization in vivo and in vitro. Targeting hemagglutinin to Xcr1 or Clec9A induces protection from influenza challenge. Targeting Ag to surface receptors on conventional type 1 dendritic cells can enhance induction of Ab and T cell responses. However, it is unclear to what extent the targeted receptor influences the resulting responses. In this study, we target Ag to Xcr1, Clec9A, or DEC-205, surface receptors that are expressed on conventional type 1 dendritic cells, and compare immune responses in BALB/c and C57BL/6 mice in vitro and in vivo after intradermal DNA vaccination. Targeting hemagglutinin from influenza A to Clec9A induced Ab responses with higher avidity that more efficiently neutralized influenza virus compared with Xcr1 and DEC-205 targeting. In contrast, targeting Xcr1 resulted in higher IFN-γ+CD8+ T cell responses in spleen and lung and stronger cytotoxicity. Both Clec9A and Xcr1 targeting induced Th1-polarized Ab responses, although the Th1 polarization of CD4+ T cells was more pronounced after Xcr1 targeting. Targeting DEC-205 resulted in poor Ab responses in BALB/c mice and a more mixed Th response. In an influenza challenge model, targeting either Xcr1 or Clec9A induced full and long-term protection against influenza infection, whereas only partial short-term protection was obtained when targeting DEC-205. In summary, the choice of targeting receptor, even on the same dendritic cell subpopulation, may strongly influence the resulting immune response, suggesting that different targeting strategies should be considered depending on the pathogen.

中文翻译:

将抗原靶向传统 1 型树突细胞上的不同受体会影响免疫反应

关键点针对 cDC1 上的不同受体会影响免疫反应。靶向 Xcr1 在体内和体外诱导 Th1 极化。将血凝素靶向 Xcr1 或 Clec9A 可诱导对流感攻击的保护。将 Ag 靶向常规 1 型树突细胞上的表面受体可以增强对 Ab 和 T 细胞反应的诱导。然而,目前还不清楚目标受体在多大程度上影响了由此产生的反应。在这项研究中,我们将 Ag 靶向 Xcr1、Clec9A 或 DEC-205(在常规 1 型树突细胞上表达的表面受体),并在皮内 DNA 后在体外和体内比较 BALB/c 和 C57BL/6 小鼠的免疫反应接种疫苗。与靶向 Xcr1 和 DEC-205 相比,将甲型流感的血凝素靶向 Clec9A 以更高的亲和力诱导抗体反应,可以更有效地中和流感病毒。相反,靶向 Xcr1 导致脾脏和肺中更高的 IFN-γ+CD8+ T 细胞反应和更强的细胞毒性。Clec9A 和 Xcr1 靶向均诱导 Th1 极化的 Ab 反应,尽管在 Xcr1 靶向后 CD4+ T 细胞的 Th1 极化更为明显。靶向 DEC-205 导致 BALB/c 小鼠的 Ab 反应较差,并且 Th 反应更加混合。在流感攻击模型中,靶向 Xcr1 或 Clec9A 诱导针对流感感染的全面和长期保护,而靶向 DEC-205 时仅获得部分短期保护。总之,靶向受体的选择,即使在相同的树突细胞亚群上,
更新日期:2020-06-26
down
wechat
bug