Release kinetics and cell trafficking in relation to bacterial growth explain the time course of blood neutrophils and monocytes during primary Salmonella infection

Abstract

Granulocytes and neutrophils are predominantly responding cells during the early phase of infection of rats with Salmonella. We propose mathematical and experimental models of the kinetics of neutrophil and monocyte responses in Salmonella infection via the oral route. Using the models, we estimate that approximately 1 in 500 inoculated Salmonella cells actually infected the rat and multiplied with a doubling time of 5 h in Peyer's patches, reaching a maximum of approximately 10(6) c.f.u./g. In low-dose infection, neutrophil and monocyte responses are delayed, but further resemble the responses in high-dose infection. Important processes influencing neutrophil and monocyte recruitment are: massive migration into the infected tissue, and non-linear release kinetics of neutrophils and monocytes from the bone marrow. In conclusion, we can predict time series of neutrophil and monocyte responses in low-dose and high-dose experimental infection via the oral route.