Streptococcus suis Capsular Polysaccharide Inhibits Phagocytosis through Destabilization of Lipid Microdomains and Prevents Lactosylceramide-Dependent Recognition

Abstract

Streptococcus suis type 2 is a major swine pathogen and a zoonotic agent, causing meningitis in both swine and humans. S. suis infects the host through the respiratory route, reaches the bloodstream, and persists until breaching into the central nervous system. The capsular polysaccharide (CPS) of S. suis type 2 is considered a key virulence factor of the bacteria. Though CPS allows S. suis to adhere to the membrane of cells of the immune system, it provides protection against phagocytosis. In fact, nonencapsulated mutants are easily internalized and killed by macrophages and dendritic cells. The objective of this work was to study the molecular mechanisms by which the CPS of S. suis prevents phagocytosis. By using latex beads covalently linked with purified CPS, it was shown that CPS itself was sufficient to inhibit entry of both latex beads and bystander fluorescent beads into macrophages. Upon contact with macrophages, encapsulated S. suis was shown to destabilize lipid microdomains at the cell surface, to block nitric oxide (NO) production during infection, and to prevent lactosylceramide accumulation at the phagocytic cup during infection. In contrast, the nonencapsulated mutant was easily internalized via lipid rafts, in a filipin-sensitive manner, leading to lactosylceramide recruitment and strong NO production. This is the first report to identify a role for CPS in lipid microdomain stability and to recognize an interaction between S. suis and lactosylceramide in phagocytes.

Role of Capsule and Suilysin in Mucosal Infection of Complement-Deficient Mice with Streptococcus suis

“…This result is in accordance with previous in vitro findings of different groups showing that unencapsulated S. suis mutants are killed by different immune cells in the presence of inactivated serum (19,20,28). Interestingly, it has been shown that the capsule inhibits phagocytosis by macrophages through destabilization of lipid microdomains (38). This complement-independent immune evasion function of the capsule might, at least partially, explain the attenuation of the unencapsulated mutant in complement-deficient mice.…”

Rapid Visual Detection of Highly Pathogenic Streptococcus suis Serotype 2 Isolates by Use of Loop-Mediated Isothermal Amplification

“…In recent years, several virulence-associated biomarkers, such as CPS, muramidase-released protein, and extracellular factor, have been used for the detection of S. suis 2 infection. However, whether these factors are associated with bacterial pathogenicity remains controversial (32,33). The identification of 89K PAI is an important factor for evaluating S. suis 2 virulence.…”

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

“…The degree of oxidation of the sialic acid (Neu5Ac) residues was assessed by gas chromatography (GC) analysis of the peracetylated methyl glycosides adapted from a previously described method (32). Briefly, oxidized CPS (0.4 mg) was reduced by treatment with 100 l of NaBH 4 (10 mg/ml) in water for 1 h at room temperature.…”