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Our aim was to investigate the quantitative relationship between inoculation doses and physiological responses to infection by Salmonella enterica serovar Enteritidis. Rats were orally inoculated with 10-10(9) c.f.u. of S. Enteritidis and monitored for 6 days. Neutrophil and delayed-type hypersensitivity (DTH) responses were assessed, and the spleens were analyzed for the pathogen. The experimental data were analyzed by a mathematical model for the host response to salmonella infection, which is based on the assumptions that: (i) the number of pathogens in the inoculum is Poisson distributed, (ii) any cell that is inoculated can multiply and form a clone to infect the animal, (iii) the probability of infection by any cell of the pathogen is independent of the number of cells ingested, and (iv) the magnitude of the immune response increases with dose, but eventually saturates to a maximum level. The probability of infection assessed by the DTH response is 7.5 x 10(-3)/c.f.u. of the inoculum (confidence interval 5.1 x 10(-5), 1.2 x 10(-2)). When five S. Enteritidis independently initiated the infection, the DTH response to the resulting clones of the salmonellae saturated to the maximum level. The probability of infection assessed by the neutrophil response is 3.4 x 10(-4)/c.f.u. (1.0 x 10(-4), 6.8 x 10(-4)). The response saturated when six S. Enteritidis independently initiated the infection. The probability of infection assessed by the analysis of spleens is 1.2 x 10(-3)/c.f.u. (4.1 x 10(-4), 2.6 x 10(-3)). We conclude that at low inocula, infections are initiated by very small numbers of bacteria. The magnitude of the immune responses is similar whether only a few or a larger number of bacteria initiated the infection.

international immunology

A quantitative model for neutrophil response and delayed-type hypersensitivity reaction in rats orally inoculated with various doses of Salmonella Enteritidis