Streptococcus suis and group B Streptococcus (GBS) are two encapsulated bacteria that induce similar pathologies, including septicemia and meningitis in animals and/or humans. Among several serotypes identified, S. suis types 2 and 14 and GBS types III and V are highly virulent and frequently isolated, and were used in our studies as a model. For both pathogens, the capsular polysaccharide (CPS), which defines the serotype, is considered as a major virulence factor. The four CPSs share structural features, including a side chain terminated by sialic acid, a unique characteristic of S. suis and GBS among Gram-positive bacteria. However, the interplay of CPS with components of the innate immune system, including antigen-presenting cells (APCs), seems to radically differ between these two streptococci. Experiments using nonencapsulated mutants have shown that, in contrast to GBS, S. suis CPS has a strong antiphagocytic effect and severely interferes with the activation and maturation of APCs and downstream modulation of NK and T cells. The anti-CPS antibody response of infected- or purified CPS-immunized mice also differs between these species/serotypes. The presence of sialic acid either contributes to CPS immunogenicity (GBS type III) or it has no impact on the antibody response depending on the CPS type. In conclusion, in spite of similar CPS biochemical features, including expression of sialic acid, S. suis and GBS differentially modulate host innate and adaptive immune responses.