Antigen I/II Participates in the Interactions of Streptococcus suis Serotype 9 With Phagocytes and the Development of Systemic Disease

Abstract

Streptococcus suis is an important porcine bacterial pathogen and a zoonotic agent causing a variety of pathologies including sudden death, septic shock, and meningitis. Though serotype 2 is the most studied serotype due to its presence worldwide, serotype 9 is responsible for the greatest number of porcine cases in Spain, the Netherlands, and Germany. Regardless of its increasing importance, very few studies have investigated S. suis serotype 9 virulence factors and pathogenesis. Antigens I/II (AgI/II) are multimodal adhesion proteins implicated in host respiratory tract and oral cavity persistence of various pathogenic human streptococci. It was recently demonstrated that AgI/II is involved in various bacterial functions for serotype 9, participating in the initial steps of the pathogenesis of the infection. However, its contribution to the systemic infection remains unknown. As such, we evaluated herein the role of the S. suis serotype 9 AgI/II in the interactions with phagocytes and the development of systemic disease in a mouse model of infection. Results demonstrated that the presence of AgI/II is important for the development of clinical systemic disease by promoting bacterial survival in blood possibly due to its effect on S. suis phagocytosis, as shown with macrophages and dendritic cells. Furthermore, AgI/II directly participates in dendritic cell activation and pro-inflammatory mediator production following recognition by the Toll-like receptor pathway, which may contribute to the exacerbated systemic inflammation responsible for host death. Taken together, this study demonstrates that the S. suis serotype 9 AgI/II is important for virulence during systemic infection and development of disease. In fact, this is the first study to describe a role of an AgI/II family member in systemic bacterial disease.

Interactions of Streptococcus suis serotype 9 with host cells and role of the capsular polysaccharide: Comparison with serotypes 2 and 14

“…Furthermore, exacerbated inflammation is a hallmark of the S . suis -induced systemic infection and is responsible for host death due to septic shock [11, 36]. In accordance, plasmatic levels of the different pro-inflammatory mediators (IL-6, IL-12p70, IFN-γ, CCL2, CCL3, CCL4, CCL5, and CXCL2) were elevated in mice infected with the serotype 9 wild-type strain (Fig 9).…”

“…To better explain differences in virulence, and since S . suis systemic infection is associated with persistent bacteremia [11, 36], blood bacterial burden was evaluated 12 h and 24 h post-infection. All mice infected with the wild-type strain presented elevated blood bacterial burdens that averaged 5 x 10 8 CFU/mL (Fig 8B and 8C).…”

“…Though serotype 9 induced lower pro-inflammatory mediator production from DCs, its immunostimulatory potential remains notable since 100% of mice infected with the wild-type strain developed septic shock within 48 h of infection, with elevated systemic inflammatory markers already observed 12 h post-infection. This does not seem to be specific to the mouse strain used, since similarly high systemic inflammation was also observed in C57BL/6 mice following infection with the same strain [11]. Interestingly, the levels of plasma mediators induced by serotype 9 are generally comparable to those induced by the serotype 2 31533 strain in CD-1 mice and the serotype 2 P1/7 strain, used herein, in C57BL/6 mice, while no results are available for serotype 14 [36, 37].…”

“…Plasmatic concentrations of IL-6, IL-12p70, interferon (IFN)-γ, CCL2, CCL3, CCL4, CCL5, and CXCL2 were measured using a custom-made cytokine Bio-Plex Pro ™ assay (Bio-Rad, Hercules, CA, USA) according to the manufacturer’s instructions. Mediators were selected based on serotype 2 and serotype 9 studies and represent the most important pro-inflammatory cytokines and chemokines secreted [11, 35–38]. Acquisition was performed on the MAGPIX platform (Luminex ® ) and data analyzed using the Bio-Plex Manager 6.1 software (Bio-Rad).…”

PCV2 aggravated SS2 infection directly showed from differentially expressed proteome of PK15 cells

“…Our results demonstrated that PCV2 cause apoptosis for it induce the chaperonin containing tailless complex polypeptide 1 decrease 59 and supplemented pathways like Wnt/Ca 2+ , and SS2 could binding to cell extracellular secreted protein 60,61 though EMC-receptor interaction. PCV2 caused cell catabolism was greater than anabolic, while SS2 caused a violent cell response.…”