Group B Streptococcus and Streptococcus suis Capsular Polysaccharides Induce Chemokine Production by Dendritic Cells via Toll-Like Receptor 2- and MyD88-Dependent and -Independent Pathways

Abstract

bStreptococcus agalactiae (also known as group B Streptococcus [GBS]) and Streptococcus suis are encapsulated streptococci causing severe septicemia and meningitis. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. The mechanisms underlying anti-CPS antibody responses are not fully elucidated, but the biochemistry of CPSs, particularly the presence of sialic acid, may have an immunosuppressive effect. We investigated the ability of highly purified S. suis and GBS native (sialylated) CPSs to activate dendritic cells (DCs), which are crucial actors in the initiation of humoral immunity. The influence of CPS biochemistry was studied using CPSs extracted from different serotypes within these two streptococcal species, as well as desialylated CPSs. No interleukin-1␤ (IL-1␤), IL-6, IL-12p70, tumor necrosis factor alpha (TNF-␣), or IL-10 production was observed in S. suis or GBS CPS-stimulated DCs. Moreover, these CPSs exerted immunosuppressive effects on DC activation, as a diminution of gamma interferon (IFN-␥)-induced B cell-activating factor of the tumor necrosis factor family (BAFF) expression was observed in CPS-pretreated cells. However, S. suis and GBS CPSs induced significant production of CCL3, via partially Toll-like receptor 2 (TLR2)-and myeloid differentiation factor 88 (MyD88)-dependent pathways, and CCL2, via TLR-independent mechanisms. No major influence of CPS biochemistry was observed on the capacity to induce chemokine production by DCs, indicating that DCs respond to these CPSs in a patterned way rather than a structure-dedicated manner.

Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine

“…Using highly purified CPS from S. suis type 2 containing less than 1% (wt/wt) of proteins or nucleic acids (as previously described by Calzas et al [30]), we investigated whether conjugation to a carrier protein, such as TT, would circumvent the TI antigenicity of the CPS and instead induce a TD protective humoral response in animals.…”

“…Due to its high M w , found to be between 410,000 and 480,000 Da by SEC-MALS (28,30), the native polysaccharide of S. suis type 2 must first be depolymerized into smaller fragments. This reduces polydispersity and yields higher ratios of polysaccharide to protein following coupling.…”

“…Capsular polysaccharides are considered TI antigens, as they are in general unable to stimulate MHC class II-dependent Th cell help (30), which results in poor immunogenicity. In contrast to TD antigens, TI antigens do not induce the classical antibody isotype switch and high-affinity memory B cells (54).…”

“…Bacterial cultures were performed as described by Calzas et al (30). CPS extraction and purification, followed by quality control procedures comprising protein determination with the modified Lowry protein assay kit (Pierce, Rockford, IL), nucleic acid quantification using an ND-1000 spectrometer (NanoDrop, Wilmington, DE), and one-dimensional (1D)/2D 1 H nuclear magnetic resonance (NMR) analysis to ensure purity and identity were performed as described by Van Calsteren et al (28).…”

The NOD2 receptor modulates the cytokine response but does not alter the clinical outcome of Group B Streptococcus-infected mice

“…Encapsulated GBS interaction with lipid rafts might also facilitate bacterial contact with caveolin-1, leading to modulation of caveolin-related signaling pathways and activation of specific immune mediators, for instance CCL2 [37] . We also observed that highly purified GBS CPSs induced significant production of CCL3 by DCs, via partially TLR2-and myeloid differentiation factor 88 (MyD88)-dependent pathways, and CCL2, via TLR-independent mechanisms [38] . A similar pattern was observed with highly purified S. suis CPSs.…”