Human C-reactive protein is protective against fatal Salmonella enterica serovar typhimurium infection in transgenic mice

C-reactive protein (CRP) is an acute-phase protein with a well-known associ ation with infection and other inflammatory conditions. We have shown that expression of human CRP by CRP transgenic (CRPtg) mice is protective agains t lethal infection by Streptococcus pneumoniae, an effect likely mediated b y CRP's ability to bind to this gram-positive pathogen, In the present stud y we tested whether CRPtg mice are resistant to infection with Salmonella e nterica serovar Typhimurium, a gram-negative pathogen that causes the murin e equivalent of typhoid fever. CRPtg mice experimentally infected with a vi rulent Typhimurium strain lived longer and had significantly lower mortalit y than their non-tg littermates, The greater resistance of CRPtg mice could be attributed to significantly increased early (0 to 4 h) blood clearance of salmonellae and significantly decreased numbers of bacteria in the liver and spleen on day 7 postinfection, In addition, 14 days after infection wi th an avirulent Salmonella strain, the serum titer of anti-Salmonella immun oglobulin G antibodies was higher in CRPtg than non-tg mice. This study pro vides unequivocal evidence that CRP plays an important role in vivo in host defense against salmonellae during the early stages of infection. In addit ion, as the beneficial effect of CRP includes enhancement of the host's hum oral immune response, CRP may also contribute indirectly to host defense du ring later stages of infection.