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International Immunology Advance Access published online on November 29, 2004
International Immunology, doi:10.1093/intimm/dxh189
© 2004 by The Japanese Society for Immunology
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Received June 18, 2003
Accepted October 26, 2004

Article

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

Katsuhisa Takumi 1*, Johan Garssen 2, Rob de Jonge 1, Wim de Jong 3, and Arie Havelaar 1

1 Microbiological Laboratory for Health Protection, National Institute for Public Health and Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands
2 Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands; Current address: Numico-Research B.V. Headquarters, Bosrandweg 20, P.O. Box 7005, 6700 CA Wageningen, The Netherlands
3 Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

* To whom correspondence should be addressed.
Katsuhisa Takumi, E-mail: Katsuhisa.Takumi{at}rivm.nl


  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 ~106 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.

Keywords: mathematical model; Peyer's patch; rodent; Salmonella enteritidis; spleen.
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