Zymosan Induces Immune Responses Comparable with Those of Adults in Monocytes, Dendritic Cells, and Monocyte-Derived Dendritic Cells from Cord Blood.
Zymosan Induces Immune Responses Comparable with Those of Adults in Monocytes, Dendritic Cells, and Monocyte-Derived Dendritic Cells from Cord Blood.
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DOI：
10.1016/j.jpeds.2015.03.035
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发表时间：
2015-07
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通讯作者：
K. Nohmi;D. Tokuhara;D. Tachibana;M. Saito;Yuko Sakashita;A. Nakano;H. Terada;Hiroko Katayama;M. Koyama;H. Shintaku
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作者：
K. Nohmi;D. Tokuhara;D. Tachibana;M. Saito;Yuko Sakashita;A. Nakano;H. Terada;Hiroko Katayama;M. Koyama;H. Shintaku
目的研究人新生儿和成人之间Toll样受体（TLR）介导的免疫应答的差异，重点关注脐带血和成人血中单核细胞、树突状细胞（DC）和单核细胞衍生的DC（MoDC）的细胞因子谱。脂多糖（TLR 4）、Pam 3CSK 4（TLR 1/2）、鞭毛蛋白（TLR 5）、酵母聚糖（TLR 2）、聚肌苷酸：聚胞苷酸（TLR 3）、咪喹莫特（TLR 7）和CpG（TLR 9）。白细胞介素（IL）-8，IL-6，肿瘤坏死因子，IL-1β，IL-10浓度进行了分析，在培养supersonnums.ResultsCompared成人血液，脂多糖，Pam 3CSK 4-，鞭毛蛋白，和聚肌胞苷酸刺激的炎症细胞因子的产生在脐带血中的影响一般较弱的单核细胞，在DC中相当，并在MoDC升高。CpG和咪喹莫特刺激的细胞因子的生产在DC中是相当的脐带血和成人血液，但细胞因子的生产几乎不存在于单核细胞和MoDC在脐带血和成人血液。相比之下，酵母多糖刺激产生可比的炎症细胞因子的配置文件中的单核细胞，树突状细胞，和MoDCs的脐带血和成人blood.ConclusionThe不成熟的TLR介导的先天免疫在新生儿依赖于单核细胞，而不是在DC。我们的研究结果表明，酵母多糖介导的TLR 2信号可能是有用的开发新生儿疫苗佐剂。
ObjectiveTo investigate the differences in toll-like receptor (TLR)-mediated immune responses between human neonates and adults, focusing on the cytokine profiles of monocytes, dendritic cells (DCs), and monocyte-derived DCs (MoDCs) in cord and adult blood.Study designPurified monocytes, DCs, and MoDCs were stimulated with the following TLR ligands: lipopolysaccharide (TLR4), Pam3CSK4 (TLR1/2), flagellin (TLR5), zymosan (TLR2), polyinosinic:polycytidylic acid (TLR3), imiquimod (TLR7), and CpG (TLR9). Interleukin (IL)-8, IL-6, tumor necrosis factor, IL-1β, and IL-10 concentrations were analyzed in culture supernatants.ResultsCompared with the effects in adult blood, lipopolysaccharide-, Pam3CSK4-, flagellin-, and polyinosinic:polycytidylic acid-stimulated inflammatory cytokine production in cord blood was generally weak in monocytes, comparable in DCs, and elevated in MoDCs. CpG- and imiquimod-stimulated cytokine production in DCs was comparable in cord blood and adult blood, but cytokine production was almost absent in monocytes and MoDCs in both cord blood and adult blood. In contrast, zymosan stimulation produced comparable inflammatory cytokine profiles in the monocytes, DCs, and MoDCs of cord blood and adult blood.ConclusionThe immaturity of TLR-mediated innate immunity in neonates depends on monocytes rather than on DCs. Our results indicate that zymosan-mediated TLR2 signaling may be useful for developing a neonatal vaccine adjuvant.