Role of capsular polysaccharide in Group B Streptococccus interactions with dendritic cells

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.