Potent induction of antibody-secreting B cells by human dermal-derived CD14+ dendritic cells triggered by dual TLR ligation.
Potent induction of antibody-secreting B cells by human dermal-derived CD14+ dendritic cells triggered by dual TLR ligation.
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DOI：
10.4049/jimmunol.1200601
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发表时间：
2012-12-15
期刊：
影响因子：
--
通讯作者：
Sanders RW
中科院分区：
文献类型：
--
作者：
Matthews K;Chung NP;Klasse PJ;Moore JP;Sanders RW
靶向CD14+真皮源性树突状细胞（ddc）是一种旨在改善体液免疫反应的疫苗接种策略的合理方法，因为它们具有刺激naïve b细胞的天然能力。在这里，我们发现CD14+ ddc表达TLRs 1-9的mRNA，但对单个或成对的TLR配体的反应不同。与单一配体相比，一些组合在激活CD14+ ddc方面特别有效，如b细胞刺激因子（IL-6、IL-10和TNF-α）的表达增强和更明显的表型成熟所示。这些组合是瑞西喹莫特（R-848）加多肌苷：多胞酸（Poly(I:C)）；R-848加LPS；Pam3CSK4 + Poly(I:C)；LPS + Poly（I:C）。我们还发现，选定的TLR配体对（R-848加LPS或Poly(I:C)）在促进CD14+ ddc诱导naïve b细胞增殖和分化为分泌高水平IgG和IgA的CD27+ CD38+ b细胞的内在能力方面优于单个药物。当使用相同的TLR配体组合处理时，CD14+ ddc也促进Th1（分泌IFN-γ） CD4+ t细胞的分化，但不促进Th2或Th17 CD4+ t细胞的分化。这些观察结果可能有助于确定旨在诱导对各种病原体（包括但不限于HIV-1）的保护性免疫反应的佐剂策略。
Targeting CD14+ dermal-derived dendritic cells (DDCs) is a rational approach for vaccination strategies aimed at improving humoral immune responses, because of their natural ability to stimulate naïve B-cells. Here, we show that CD14+ DDCs express mRNA for TLRs 1–9, but respond differentially to single or paired TLR ligands. Compared to single ligands, some combinations were particularly effective at activating CD14+ DDCs, as shown by enhanced expression of B-cell stimulatory cytokines (IL-6, IL-10 and TNF-α) and more pronounced phenotypic maturation. These combinations were Resiquimod (R-848) plus Polyinosinic:polycytidylic acid (Poly(I:C)); R-848 plus LPS; Pam3CSK4 plus Poly(I:C); LPS plus Poly(I:C). We also found that selected TLR ligand pairs (R-848 plus either LPS or Poly(I:C)) were superior to individual agents at boosting the inherent capacity of CD14+ DDCs to induce naïve B-cells to proliferate and differentiate into CD27+ CD38+ B-cells that secrete high levels of IgG and IgA. When treated with the same TLR ligand combinations, CD14+ DDCs also promoted the differentiation of Th1 (IFN-γ-secreting) CD4+ T-cells, but not of Th2 or Th17 CD4+ T-cells. These observations may help to identify adjuvant strategies aimed at inducing protective immune responses to various pathogens, including but not limited to HIV-1.
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I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
DOI：
10.1084/jem.20081633
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Haniffa M;Ginhoux F;Wang XN;Bigley V;Abel M;Dimmick I;Bullock S;Grisotto M;Booth T;Taub P;Hilkens C;Merad M;Collin M
通讯作者：
Collin M
影响因子：
20.3
作者：
Banchereau, Jacques;Thompson-Snipes, Luann;Klechevsky, Eynav
通讯作者：
Klechevsky, Eynav
DOI：
10.1073/pnas.1103869108
发表时间：
2011-04-26
影响因子：
11.1
作者：
Flynn, Barbara J.;Kastenmueller, Kathrin;Seder, Robert
通讯作者：
Seder, Robert
影响因子：
4.4
作者：
Douagi, Iyadh;Gujer, Cornelia;Lore, Karin
通讯作者：
Lore, Karin