CpG Oligodeoxinucleotides and Flagellin Modulate the Immune Response to Antigens Targeted to CD8α(+) and CD8α(-) Conventional Dendritic Cell Subsets.
CpG Oligodeoxinucleotides and Flagellin Modulate the Immune Response to Antigens Targeted to CD8α(+) and CD8α(-) Conventional Dendritic Cell Subsets.
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DOI：
10.3389/fimmu.2017.01727
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发表时间：
2017
影响因子：
7.3
通讯作者：
Boscardin SB
中科院分区：
文献类型：
--
作者：
Antonialli R;Sulczewski FB;Amorim KNDS;Almeida BDS;Ferreira NS;Yamamoto MM;Soares IS;Ferreira LCS;Rosa DS;Boscardin SB
树突状细胞是抗原呈递细胞，对诱导适应性免疫应答至关重要。它们向T细胞呈递抗原的能力前所未有，这使它们成为疫苗开发的绝佳目标。在过去的几年里，一种基于抗原直接递送到不同DC亚群的新技术，通过使用混合单克隆抗体（mab）将DC表面受体与感兴趣的抗原融合，为诱导强大的免疫反应开辟了新的视角。通常，杂交单克隆抗体与诱导DC成熟的佐剂一起施用。在这项工作中，我们分别使用杂交αDEC205或αDCIR2单抗，在CpG寡脱氧核苷酸（ODN）或细菌鞭毛蛋白存在的情况下，将抗原靶向CD8α+或CD8α−DC亚群。我们还研究了toll样受体（TLRs） 5和9信号在诱导特异性体液和细胞免疫应答中的作用。将野生型和TLR5或TLR9敲除小鼠分别接种两剂杂交αDEC205或αDCIR2单抗，以及同型对照，并与CpG ODN 1826或鞭毛蛋白一起免疫。将含有与泛等位基因DR表位连接的间日疟原虫子粒表面蛋白（MSP119） 19kda部分的嵌合抗原融合到每个单抗上。分析特异性CD4+ T细胞增殖、细胞因子和抗体产生。我们发现CpG ODN 1826或鞭毛蛋白能够诱导CD4+ T细胞增殖，当抗原靶向CD8α+ DC亚群时，CD4+ T细胞产生促炎细胞因子和特异性抗体。另一方面，靶向CD8α - DC亚群的抗原促进了特异性抗体反应和增殖，但没有检测到促炎CD4+ T细胞反应。此外，在缺乏TLR9或TLR5信号的情况下，抗原靶向CD8α+或CD8α - dc后的特异性抗体反应降低，而CD4+ T细胞的增殖主要受到抗原靶向CD8α+ dc和缺乏TLR9信号的影响。这些结果扩展了我们对不同佐剂存在下抗原靶向dc诱导的特异性免疫反应的调节的理解。这些知识可能有助于优化基于dc的疫苗。
Dendritic cells (DCs) are antigen-presenting cells essential for the induction of adaptive immune responses. Their unprecedented ability to present antigens to T cells has made them excellent targets for vaccine development. In the last years, a new technology based on antigen delivery directly to different DC subsets through the use of hybrid monoclonal antibodies (mAbs) to DC surface receptors fused to antigens of interest opened new perspectives for the induction of robust immune responses. Normally, the hybrid mAbs are administered with adjuvants that induce DC maturation. In this work, we targeted an antigen to the CD8α+ or the CD8α− DC subsets in the presence of CpG oligodeoxinucleotides (ODN) or bacterial flagellin, using hybrid αDEC205 or αDCIR2 mAbs, respectively. We also accessed the role of toll-like receptors (TLRs) 5 and 9 signaling in the induction of specific humoral and cellular immune responses. Wild-type and TLR5 or TLR9 knockout mice were immunized with two doses of the hybrid αDEC205 or αDCIR2 mAbs, as well as with an isotype control, together with CpG ODN 1826 or flagellin. A chimeric antigen containing the Plasmodium vivax 19 kDa portion of the merozoite surface protein (MSP119) linked to the Pan-allelic DR epitope was fused to each mAb. Specific CD4+ T cell proliferation, cytokine, and antibody production were analyzed. We found that CpG ODN 1826 or flagellin were able to induce CD4+ T cell proliferation, CD4+ T cells producing pro-inflammatory cytokines, and specific antibodies when the antigen was targeted to the CD8α+ DC subset. On the other hand, antigen targeting to CD8α− DC subset promoted specific antibody responses and proliferation, but no detectable pro-inflammatory CD4+ T cell responses. Also, specific antibody responses after antigen targeting to CD8α+ or CD8α− DCs were reduced in the absence of TLR9 or TLR5 signaling, while CD4+ T cell proliferation was mainly affected after antigen targeting to CD8α+ DCs and in the absence of TLR9 signaling. These results extend our understanding of the modulation of specific immune responses induced by antigen targeting to DCs in the presence of different adjuvants. Such knowledge may be useful for the optimization of DC-based vaccines.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
7.3
作者：
Apostólico JS;Lunardelli VA;Yamamoto MM;Souza HF;Cunha-Neto E;Boscardin SB;Rosa DS
通讯作者：
Rosa DS
CpG寡脱氧核苷酸纳米药物用于预防或治疗癌症，传染病和过敏。
影响因子：
8
作者：
Hanagata N
通讯作者：
Hanagata N
影响因子：
4.1
作者：
Amorim KN;Chagas DC;Sulczewski FB;Boscardin SB
通讯作者：
Boscardin SB
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC