Evaluation of the pathogenesis of meningitis caused by Streptococcus suis sequence type 7 using the infection of BV2 microglial cells

Abstract

Streptococcus suis is an important agent of swine and human meningitis. Among several sequence types (STs) characterized within the S. suis strain population, ST7 has emerged only in China and has been reported to be the cause of the human outbreak caused by S. suis in 2005. S. suis ST7 was shown to be derived from S. suis ST1 through a single-nucleotide change in the housekeeping gene thyA. The virulence potential of S. suis ST7 is reported to be higher than that of the worldwide-studied pathogenic S. suis ST1. The pathogenesis of ST1 infection has been partially elucidated, but information on the pathogenesis of ST7 infections remains scarce. To improve our understanding of the mechanisms involved in the development of meningitis caused by ST7, this study compared the microglial inflammatory response induced by ST1 and ST7 strains. The data showed that S. suis ST7 possessed a higher ability to induce pro-inflammatory cytokine production and to activate mitogen-activated protein kinase pathways and several transcription factors. The stimulation of microglial cells by S. suis increased the expression levels of the nucleotide oligomerization domain 2 (Nod2) gene. Finally, the results indicated that signal transducer and activator of transcription 3 (STAT-3) was involved in the development of meningitis induced by S. suis ST7 infection.

Comparative Genomic Hybridization Identifies Virulence Differences in Streptococcus suis

“…TLR2/6 is involved in the recognition of S. suis by the immune system[15], [16], [17], [18]. Here we found there was a correlation between the capacity to induce TLR2/6 signaling and the virulence level.…”

“…Induction of TNF-α and MCP-1 by S. suis play an important role in the pathogenesis of S. suis [10], [11], [15]. Strains with blood bacterial loads <10 5 did not induce obvious cytokine production (data not shown).…”

“…TLR2/6 plays an important role in inducing cytokine production by S. suis [15], [16], [17], [18]. We used 293-hTLR2/6 cells to investigate whether the 17 strains with >10 5 blood bacterial load in mouse infections possessed different capacities to activate TLR2/6 signaling by determining the amount of IL-8 induced.…”

Streptococcus suis: a re-emerging pathogen associated with occupational exposure to pigs or pork products. Part II – Pathogenesis

“…The above-cited results were further confirmed by Zheng et al [33] who infected the BV2 cell line, a substitute for primary microglia cells, with the S. suis highly pathogenic strain ST7 (sequence type 7) which caused a major epidemics in China in 2005, and with the pathogenic strain ST1. They proved that the ST7 strain induced a greater microglial inflammatory response compared to ST1, as shown by a higher pro-inflammatory cytokine production, as well as by higher activation of MAPK signaling pathways and several transcription factors.…”

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

“…Many in vitro or in vivo studies established that NOD2 is a relevant mediator of host defense against a wide range of pathogens, including intracellular bacteria like Listeria monocytogenes [6,7] , Mycobacterium tuberculosis [8][9][10] , Neisseria gonorrhoeae [11] , Helicobacter pylori [12] and Legionella pneumophila [13] . NOD2 has also been shown to regulate the immune response to extracellular bacteria, such as Streptococcus pneumoniae [14][15][16] , Streptococcus pyogenes [17] , Streptococcus suis [18,19] and Staphylococcus aureus [20][21][22][23][24][25] .…”