Streptococcus suis Serotype 2, an Important Swine and Human Pathogen, Induces Strong Systemic and Cerebral Inflammatory Responses in a Mouse Model of Infection

Abstract

Streptococcus suis, an important swine and human pathogen, causes septic shock and meningitis. The pathogenesis of both systemic and CNS infections caused by S. suis is poorly understood. A hematogenous model of infection in CD1 mice was developed to study the systemic release of cytokines during the septic shock phase and the proinflammatory events in the CNS associated with this pathogen. Using a liquid array system, high levels of systemic TNF-α, IL-6, IL-12, IFN-γ, CCL2, CXCL1, and CCL5 were observed 24 h after infection and might be responsible for the sudden death of 20% of animals. Infected mice that survived the early sepsis later developed clinical signs of meningitis and exhibited lesions in the meninges and in numerous regions of the brain, such as the cortex, hippocampus, thalamus, hypothalamus, and corpus callosum. Bacterial Ags were found in association with microglia residing only in the affected zones. In situ hybridization combined with immunocytochemistry showed transcriptional activation of TLR2 and TLR3 as well as CD14, NF-κB, IL-1β, CCL2, and TNF-α, mainly in myeloid cells located in affected cerebral structures. Early transcriptional activation of TLR2, CD14, and inflammatory cytokines in the choroid plexus and cells lining the brain endothelium suggests that these structures are potential entry sites for the bacteria into the CNS. Our data indicate an important role of the inflammatory response in the pathogenesis of S. suis infection in mice. This experimental model may be useful for studying the mechanisms underlying sepsis and meningitis during bacterial infection.

Exacerbated Type II Interferon Response Drives Hypervirulence and Toxic Shock by an Emergent Epidemic Strain of Streptococcus suis

“…In agreement with the findings of previous studies (20,21,26), patterns of bacterial burdens observed in spleen and liver were similar to those observed in blood samples, with no significant differences being detected among strains (data not shown). These results suggest that the increased virulence of S. suis ST7 cannot be explained by an increase in blood bacterial burden and that other factors account for its pathogenic potential.…”

“…Our laboratory previously developed a mouse model of S. suis systemic infection (20,21). Infected animals can succumb rapidly, and this mortality can be associated with septic shock symptoms.…”

Gamma Interferon Signaling in Macrophage Lineage Cells Regulates Central Nervous System Inflammation and Chemokine Production

“…These observations are intriguing given the purported role of IFN-␥ in the pathogenesis of several diseases, such as multiple sclerosis, sepsis, human immunodeficiency virus-associated dementia, and Alzheimer's (14,19,32,79,81). The results of the present study can lend insight into results from current clinical trials involving the administration of IFN-␥ as adjuvant therapy (49) and possibly the design of future trials involving IFN-␥ blockade.…”

The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid

“…Lecours et al (2011) showed that CPS impairs cytokine release by hindering cell wall components; thus, reduced levels of CPS could result in exposing bacterial cell wall components and facilitate an increased inflammatory response. Studies on meningitis-associated bacteria have shown that a fatal disease outcome can be caused by the host inflammatory response (Dominguez-Punaro et al 2007). Dominguez-Punaro et al (2010) showed that after being stimulated by an SS CPS-deficient mutant, the microglia induced significantly higher levels of proinflammatory mediators than that of the wild-type strain.…”