Natural resistance to Salmonella typhimurium in different inbred mouse strains

The mechanisms of natural resistance to intravenous challenge with Salmonella typhimurium C5 are complex. LD50 determinations showed inbred mouse strains of low, intermediate and high natural resistance, with BALB/c and B10 strains the most susceptible, A/J the most resistant. Delayed (footpad) hypersensitivity was not by itself a measure of natural resistance. Resistant mouse strains sensitized either s.c. or i.v. with an attenuated salmonella strain showed positive 48 h footpad reactions when tested 8 days later with a salmonella extract, but three very susceptible strains also showed positive reactions. Determinations of the in vivo net growth rate of salmonellae in the liver and spleen during the first phase of the infection (up to day 4) arrange the different mouse strains into two categories of fast and slow net growth rate. All fast net growth rate strains are susceptible, but not all slow net growth rate strains are resistant. Besides slow net growth rate, resistance requires the participation of other factors appearing in the second phase of the infection (towards the end of the first week) probably involving the cellular immune response, which halts further bacterial growth. Not all slow net growth rate strains are equally capable of suppressing bacterial growth in this second phase. The host mechanism determining slow net growth rate is inherited as a dominant trait, and appears to be operating before the main cellular immune response. The influence of this mechanism on net growth rate is reflected in the time to death following a given dose of salmonellae. The present results suggest that overall resistance to salmonellae is polygenic, but that the mechanism responsible for the differences in early net growth rate is less complex.