Streptococcus suis serotype 2, an important swine and human pathogen, induces strong systemic and cerebral inflammatory responses in a mouse model of infection.
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-alpha, IL-6, IL-12, IFN-gamma, 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-kappaB, IL-1beta, CCL2, and TNF-alpha, 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.
Domínguez-Punaro
María C
MC
Groupe de Recherche sur les Maladies Infectieuses du Porc, Faculté de médecine vétérinaire, Université de Montréal, St.-Hyacinthe, Québec, Canada.
Segura
Mariela
M
Plante
Marie-Michèle
MM
Lacouture
Sonia
S
Rivest
Serge
S
Gottschalk
Marcelo
M
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020672:I-kappa B Proteins / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D016920:Meningitis, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D013290:Streptococcal Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D017011:Streptococcus suis / Q000276:immunology*; D013552:Swine; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis
D018925:Chemokines; D016207:Cytokines; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4