How does CD8 loss impact the immune response to systemic salmonella infection?

Faustini, Siân Elizabeth (2013). How does CD8 loss impact the immune response to systemic salmonella infection? University of Birmingham. M.Res.

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Abstract

Salmonella enterica serovar Typhimurium (STm) is an intracellular, gram-negative, facultative bacteria that causes two types of infection in humans: Typhoidal and Non-typhoidal Salmonella (NTS). NTS is known to cause a self-limiting gastroenteritis in the western world. However, it can be life-threatening to immunocompromised HIV-infected and non-infected individuals living in Sub-Saharan Africa. This study aimed to characterise the impact of CD8 loss in the immune response to STm in the spleen, peritoneal cavity, and thymus though the use of a knock out mouse strain (CD8 KO) and the infection with an attenuated STm bacterial strain (SL3261). Predominantly, CD4+T-cells or Th1 cells are more important in producing IFN-γ and mediating bacterial clearance during primary infection. In contrast, the role of CD8 molecules during primary and secondary STm infection is less clear. Bacterial culture revealed that bacterial clearance is hindered at day 35 post-infection in CD8 KO mice. We observed a defect in the early extrafollicular (EF) response with regards to the production of lower levels of OMP-specific IgG at day 7 post-infection. This also inhibited isotype class-switching; thus, IgG2b and IgG2a (IgG2c in C57BL/6 mice) antibody levels were also low. Thus, the absence of CD8 molecules must impact the early TFH response during thymus-dependent (TD) antibody responses. In future experiments, it would be useful to characterise the immune response to STm in CD8 KO mice using a virulent strain of STm, SL1344 to see if primary infection with the attenuated strain allows for the conferred protection once challenged with the virulent strain.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

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