Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
J Clin Immunol. 2010 May;30(3):435-41. doi: 10.1007/s10875-010-9371-z. Epub 2010 Feb 23.
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.
肺炎链球菌是常见可变免疫缺陷（CVID）最常见的感染病原体之一。先天和适应性免疫反应似乎都在防御肺炎链球菌中发挥作用。在小鼠中，已经证实 TLR2 和巨噬细胞衍生的细胞因子（IL-6、TNF-α）在防御肺炎链球菌中起着至关重要的作用。在人类中，尚未研究针对肺炎链球菌的单核细胞/巨噬细胞衍生细胞因子。CVID 患者对 23 价肺炎球菌多糖疫苗（包含所有荚膜多糖）的反应不佳。
在这项研究中，我们表明，肺炎球菌疫苗以浓度和时间依赖性的方式诱导健康对照者的单核细胞而非 B 细胞或 T 细胞分泌 IL-6、IL-10 和 TNF-α。此外，与对照组相比，CVID 患者的肺炎球菌疫苗诱导的 IL-6 和 TNF-α 分泌显著减少。此外，肺炎球菌疫苗诱导所有四种单核细胞亚群中 TLR2 的上调；然而，对照组和 CVID 之间的差异没有统计学意义。
CVID 中肺炎球菌疫苗诱导的单核细胞衍生细胞因子产生受损，这可能在 CVID 患者对肺炎链球菌感染的易感性增加中起重要作用。
