Gamma Irradiation or CD4⁺-T-Cell Depletion Causes Reactivation of LatentSalmonella entericaSerovar Typhimurium Infection in C3H/HeN Mice

Abstract

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.

The capacity ofSalmonellato survive inside dendritic cells and prevent antigen presentation to T cells is host specific

“…Supporting this notion is the observation that S . Typhimurium induces a strong immune response in other hosts, such as chickens and humans, 37–39 and can only cause a systemic disease when cellular adaptive immunity is deficient in these hosts 40–42 …”

“…35,36 Supporting this notion is the observation that S. Typhimurium induces a strong immune response in other hosts, such as chickens and humans, [37][38][39] and can only cause a systemic disease when cellular adaptive immunity is deficient in these hosts. [40][41][42] Dendritic cells play a crucial role in initiating adaptive immunity in the host, capturing Salmonella at an early stage of infection, so interference with the ability of DCs to process and present bacterial antigens could be advantageous for Salmonella dissemination within its specific host. Accordingly, it is likely that Salmonella serovars that fail to cause disease within a specific host could also be unable to interfere with DC function, which would then result in the activation of the adaptive immune response and bacterial clearance.…”

Microscopic Detection of ViableStaphylococcus epidermidisin Peri-Implant Tissue in Experimental Biomaterial-Associated Infection, Identified by Bromodeoxyuridine Incorporation

“…van Diepen et al (39) used gamma irradiation to reactivate Salmonella enterica serovar Typhimurium infection in a mouse intestinal infection model at a time point when bacteria were undetectable by culture. After total body irradiation, the numbers of bacteria in liver and spleen increased to numbers similar to those in the primary infection, indicating that by gamma irradiation, assumed to cause immunosuppression, reactivation of a Salmonella infection can take place.…”

Pseudoloma neurophiliaInfection Combined with Gamma Irradiation Causes Increased Mortality in Adult Zebrafish (Danio rerio) Compared to Infection or Irradiation Alone: New Implications for Studies Involving Immunosuppression

“…27 The effects of gamma irradiation on secondary infections is also well-documented in the laboratory mouse, which is susceptible to both latent infection activation and novel infection by otherwise lowvirulence pathogens. 29,30 There was a general trend of increased severity of infection based on abundance of CNS parasites, non-CNS infections, and myositis. However, even with 2-3 times increase on particular endpoints the change was not always statistically significant.…”