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* Groupe de Recherche sur les Maladies Infectieuses du Porc, Faculté de médecine vétérinaire, Université de Montréal, St.-Hyacinthe, Québec, Canada;
Laboratory of Molecular Endocrinology, Centre Hospitalier de l’Université Laval, St.-Foy, Québec, Canada; and
Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
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-
, IL-6, IL-12, IFN-
, 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-
B, IL-1
, CCL2, and TNF-, 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Natural Sciences and Engineering Research Council of Canada Grant 0680154280, Canadian Institutes of Health Research (to S.R.), and Centre de recherche en infectiologie porcine (Fonds québécois de la recherche sur la nature et les technologies).
2 Address correspondence and reprint requests to Dr. Marcelo Gottschalk, Groupe de Recherche sur les Maladies Infectieuses du Porc, Faculté de médecine vétérinaire, Université de Montréal, 3200 rue Sicotte, St.-Hyacinthe, Québec, J2S 2M2, Canada. E-mail address: marcelo.gottschalk{at}umontreal.ca
3 Abbreviations used in this paper: BMEC, brain microvascular endothelial cell; BBB, blood brain barrier; THB, Todd-Hewitt broth; p.i., postinfection; PFA, paraformaldehyde; DEPC, diethylpyrocarbonate; PLP, proteolipid protein; KPBS, potassium-PBS; DAB, 3,3'-diaminobenzidine; SBB, Sudan black B staining; PGN, peptidoglycan; LTA, lipoteichoic acid.
4 The online version of this article contains supplemental material.
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  N. Fittipaldi, T. Sekizaki, D. Takamatsu, J. Harel, M. d. l. C. Dominguez-Punaro, S. Von Aulock, C. Draing, C. Marois, M. Kobisch, and M. Gottschalk D-Alanylation of Lipoteichoic Acid Contributes to the Virulence of Streptococcus suis Infect. Immun., August 1, 2008; 76(8): 3587 - 3594. [Abstract] [Full Text] [PDF]
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