Laboratory of Immunology, Université de Montréal, St-Hyacinthe, J2S 2M2 Québec, Canada.
Microbes Infect. 2012 Oct;14(12):1064-76. doi: 10.1016/j.micinf.2012.05.015. Epub 2012 Jun 5.
Group B Streptococcus (GBS) type III is an important agent of life-threatening invasive infections. Albeit the immune system plays a dual role in development and protection against disease, mechanisms leading to an efficient immune response against GBS remain obscure. Mouse bone marrow-derived dendritic cells (DCs) and primary spleen DCs were used to evaluate GBS capacity to modulate the functions of these important antigen-presenting cells. The role of capsular polysaccharide (CPS), one of the most important GBS virulence factors, in bacterial-DC interactions was evaluated by using a non-encapsulated mutant. Phagocytosis assays, confocal and electron microscopy showed that DCs efficiently internalize encapsulated GBS, but the latter possesses strong intracellular survival capacity. GBS devoid of CPS was internalized and killed at higher and faster rates than encapsulated GBS early after infection. Among several cytokines tested, GBS internalization was required for modulation of IL-12, IL-10 and CXCL10 pathways. In contrast, GBS induced DC expression of co-stimulatory molecules in a phagocytosis-independent manner. Finally, the production of pro-inflammatory and Th1 cytokines by GBS-stimulated DCs was differentially modulated by CPS expression, depending on DC origin. Our data suggest multiple mechanisms involved in GBS modulation of DC functions, which were selectively regulated by the presence of CPS.
III 型 B 群链球菌（GBS）是一种严重威胁生命的侵袭性感染的重要病原体。尽管免疫系统在疾病的发展和保护中发挥着双重作用，但导致针对 GBS 产生有效免疫反应的机制仍不清楚。我们使用骨髓来源的树突状细胞（DCs）和原代脾脏 DCs 来评估 GBS 调节这些重要抗原呈递细胞功能的能力。通过使用无荚膜突变体来评估荚膜多糖（CPS）这一最重要的 GBS 毒力因子之一在细菌-DC 相互作用中的作用。吞噬作用试验、共聚焦和电子显微镜显示，DCs 能有效内化包裹的 GBS，但后者具有很强的细胞内生存能力。无荚膜的 GBS 在感染早期被内化和杀死的速度和程度均高于包裹的 GBS。在测试的几种细胞因子中，IL-12、IL-10 和 CXCL10 途径的调节需要 GBS 的内化。相比之下，GBS 以非吞噬作用的方式诱导 DC 表达共刺激分子。最后，由 GBS 刺激的 DCs 产生的促炎和 Th1 细胞因子的表达水平受 CPS 表达的调节，这取决于 DC 的来源。我们的数据表明，GBS 调节 DC 功能的机制有多种，这些机制是通过 CPS 的存在选择性调节的。
