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Gamma Irradiation or CD4⁺-T-Cell Depletion Causes Reactivation of Latent Salmonella enterica Serovar Typhimurium Infection in C3H/HeN Mice

Angela van Diepen,¹ Joke S. van de Gevel,¹ Margaretha M. Koudijs,¹ Ferry Ossendorp,² Henry Beekhuizen,¹ Riny Janssen,^1, and Jaap T. van Dissel^1,*

Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden,¹ Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands²

Received 6 September 2004/ Returned for modification 22 November 2004/ Accepted 3 January 2005

Upon infection with Salmonella, a host develops an immune response to limit bacterial growth and kill and eliminate the pathogen. Salmonella has evolved mechanisms to remain dormant within the body, only to reappear (reactivate) at a later time when the immune system is abated. We have developed an in vivo model for studying reactivation of Salmonella enterica serovar Typhimurium infection in mice. Upon subcutaneous infection, C3H/HeN (Ity^r) mice showed an increase in bacterial numbers in livers and spleens, which reached a peak on day 19. After full recovery from the infection, these mice were irradiated or depleted of CD4⁺ T cells. The mice displayed a secondary infection peak in livers and spleens with a course similar to that of the primary infection. We concluded that CD4⁺ T cells are involved in active suppression of S. enterica serovar Typhimurium during latency. The role of CD4⁺ T cells during primary infection with S. enterica serovar Typhimurium is well established. This is the first study to describe a role of CD4⁺ T cells during the latent phase of S. enterica serovar Typhimurium infection.

Editor: A. D. O'Brien

R.J. and J.T.V.D. equally contributed to this study.