Intraspecies Variability in the Dose-Response Relationship for Salmonella Enteritidis Associated with Genetic Differences in Cellular Immune Response

Abstract

To evaluate the effects of differences in host cellular immunity, we studied the dose-response relationship for infection with Salmonella enterica serovar Enteritidis (SE) in two different rat strains, skewed towards T helper 1 (Th1, Lewis rats) or T helper 2 (Th2, Brown Norway rats) immunoregulation. Rats were exposed orally to different doses of SE after overnight starvation and neutralization of gastric acid. Animals were observed for clinical signs of disease, fecal excretion and SE load in spleen and cecum, histopathology of the cecum, hematology, and cellular and humoral immune responses. Exponential dose-response models were used for binary or continuous outcomes to analyze the experimental data. Cytokine patterns, antibody isotypes, and contact hypersensitivity tests confirmed that Lewis rats are Th1 prone, whereas Brown Norway rats are Th2 prone. The probability of infection per single SE cell was approximately 100 times higher in Brown Norway rats than in Lewis rats. Cellular immune responses were more pronounced in Lewis rats but antibody responses were higher in Brown Norway rats. When infected, colonization levels and inflammation are highest in the intestinal tract of Th2 skewed rats, but systemic infection is more intense in Th1 skewed rats. Successful colonization by only one or two SE clones resulted in a marked increase of neutrophil counts by a factor of two to three in both rat strains.