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Infection and Immunity, September 2008, p. 3901-3910, Vol. 76, No. 9
0019-9567/08/$08.00+0 doi:10.1128/IAI.00350-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Groupe de Recherche sur les Maladies Infectieuses du Porc (GREMIP) and Centre de Recherche en Infectiologie Porcine (CRIP), Faculté de médecine vétérinaire, Université de Montréal, St-Hyacinthe, Quebec J2S 7C6, Canada,1 Centre for the Study of Host Resistance, McGill University Health Centre Research Institute, Montreal, Quebec H3G 1A4, Canada,2 Laboratory of Molecular Endocrinology, Centre Hospitalier de l'Université Laval, St-Foy, Quebec G1V 4H2, Canada3
Received 17 March 2008/ Returned for modification 13 May 2008/ Accepted 13 June 2008
Streptococcus suis is an important swine and human pathogen. Assessment of susceptibility to S. suis using animal models has been limited to monitoring mortality rates. We recently developed a hematogenous model of S. suis infection in adult CD1 outbred mice to study the in vivo development of an early septic shock-like syndrome that leads to death and a late phase that clearly induces central nervous system damage, including meningitis. In the present study, we compared the severities of septic shock-like syndrome caused by S. suis between adult C57BL/6J (B6) and A/J inbred mice. Clinical parameters, proinflammatory mediators, and bacterial clearance were measured to dissect potential immune factors associated with genetic susceptibility to S. suis infection. Results showed that A/J mice were significantly more susceptible than B6 mice to S. suis infection, especially during the acute septic phase of infection (100% of A/J and 16% of B6 mice died before 24 h postinfection). The greater susceptibility of A/J mice was associated with an exaggerated inflammatory response, as indicated by their higher production of tumor necrosis factor alpha, interleukin-12p40/p70 (IL-12p40/p70), gamma interferon, and IL-1β, but not with different bacterial loads in the blood. In addition, IL-10 was shown to be responsible, at least in part, for the higher survival in B6 mice. Our findings demonstrate that A/J mice are very susceptible to S. suis infection and provide evidence that the balance between pro- and anti-inflammatory mediators is crucial for host survival during the septic phase.
Published ahead of print on 23 June 2008.
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