Abstract

Streptococcus suis is an encapsulated bacterium and one of the most important swine pathogens and a zoonotic agent for which no effective vaccine exists. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. In addition to the previously known serotypes 2 and 14, which are nonimmunogenic, we have recently purified and described the CPS structures for serotypes 1, 1/2, 3, 7, 8, and 9. Here, we aimed to elucidate how these new structurally diverse CPSs interact with the immune system to generate anti-CPS antibody responses. CPS-stimulated dendritic cells produced significant levels of C-C motif chemokine ligand 3 (CCL3), partially via Toll-like receptor 2 (TLR2)- and myeloid differentiation factor 88-dependent pathways, and CCL2, via TLR-independent mechanisms. Mice immunized with purified serotype 3 CPS adjuvanted with TiterMax Gold produced an opsonizing IgG response, whereas other CPSs or adjuvants were negative. Mice hyperimmunized with heat-killed S. suis serotypes 3 and 9 both produced anti-CPS type 1 IgGs, whereas serotypes 7 and 8 remained negative. Also, mice infected with sublethal doses of S. suis serotype 3 produced primary anti-CPS IgM and IgG responses, of which only IgM were boosted after a secondary infection. In contrast, mice sublethally infected with S. suis serotype 9 produced weak anti-CPS IgM and IgG responses following a secondary infection. This study provides important information on the divergent evolution of CPS serotypes with highly different structural and/or biochemical properties within S. suis and their interaction with the immune system.

Highlights

  • Streptococcus suis is an encapsulated bacterium and one of the most important swine pathogens and a zoonotic agent for which no effective vaccine exists

  • Results revealed that Ͻ1% of nucleic acids and proteins were detected in the purified capsular polysaccharides (CPSs) samples, with the only exception being CPS 9, which showed a striking protein content of 6.7%

  • Using the NanoOrange assay, no proteins were found above the detection limit of 0.4%, confirming that CPS 9 is free from protein and that the result obtained with the modified Lowry assay is due to an interference by its 4-keto sugar

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Summary

Introduction

Streptococcus suis is an encapsulated bacterium and one of the most important swine pathogens and a zoonotic agent for which no effective vaccine exists. S. suis is an emerging zoonotic pathogen, leading to meningitis, septic shock, and other less common clinical manifestations usually associated with generalized septicemia This zoonosis is of particular worldwide incidence in people working in close contact with infected pigs and/or pork-derived products during their professional activities [2]. Even the general population is at risk in some Asian countries, where multiple outbreaks of infection have been reported after ingestion of contaminated raw pork products [2, 3] In countries such as Vietnam and Thailand, S. suis is considered to be among the most frequent causes of bacterial meningitis in human adults [4]. As with other encapsulated pathogens such as GBS, S. pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, antibodies targeting the CPS are opsonizing and mediate protection [10,11,12]

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