Impaired Pneumovax-23-Induced Monocyte-Derived Cytokine Production in Patients with Common Variable Immunodeficiency
Impaired Pneumovax-23-Induced Monocyte-Derived Cytokine Production in Patients with Common Variable Immunodeficiency
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DOI：
10.1007/s10875-010-9371-z
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发表时间：
2010-05-01
影响因子：
9.1
通讯作者：
Gupta, Sudhir
中科院分区：
文献类型：
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作者：
Hong, Raymond;Agrawal, Sudhanshu;Gupta, Sudhir
肺炎链球菌（Streptococcus pneumoniae，SP）是常见变异型免疫缺陷病（CVID）最常见的病原体之一。先天性和适应性免疫反应似乎在抵抗S.肺炎。在小鼠中，已经确定TLR 2和巨噬细胞衍生的细胞因子（IL-6、TNF-α）在防御S.肺炎。在人类中，单核细胞/巨噬细胞源性细胞因子响应于S. pneumoniae尚未研究。CVID患者对Pneumovax-23（含有所有荚膜多糖）疫苗接种反应较差。在这项研究中，我们发现Pneumovax-23以浓度和时间依赖性方式诱导单核细胞分泌IL-6、IL-10和TNF-α，而健康对照组的B细胞或T细胞则不分泌。此外，与对照组相比，CVID患者中Pneumovax-23诱导的IL-6和TNF-α分泌显著减少。此外，Pneumovax-23诱导所有四种单核细胞亚群中TLR 2的上调;然而，对照组和CVID组之间的差异不显著。Pneumovax-23诱导的单核细胞源性细胞因子的产生在CVID中受损，这可能在CVID患者对S.肺炎感染。
Streptococcus pneumoniae is one of the most common infectious pathogens in common variable immunodeficiency (CVID). Both innate and adaptive immune response appears to play a role in defense against S. pneumoniae. In mice, it has been established that TLR2 and macrophages-derived cytokines (IL-6, TNF-alpha) play a crucial role in defense against S. pneumoniae. In humans, monocyte/macrophage-derived cytokines in response to S. pneumoniae have not been studied. Patients with CVID respond poorly to Pneumovax-23 (containing all capsular polysaccharides) vaccination.In this study, we show that Pneumovax-23, in a concentration and time-dependent manner, induced secretion of IL-6, IL-10, and TNF-alpha by monocytes and not by B cells or T cells from healthy controls. Furthermore, Pneumovax-23-induced secretion of IL-6 and TNF-alpha was significantly less in patients with CVID as compared with controls. In addition, Pneumovax-23-induced upregulation of TLR2 in all four subsets of monocytes; however, differences between control and CVID were not significant.Pneumovax-23-induced monocytes-derived cytokine production is impaired in CVID, which may play an important role in increased susceptibility of CVID patients to S. pneumoniae infection.