Date of Award
Master of Science
Molecular Biology Microbiology and Biochemistry
The spleen is an essential lymphoid organ where pathogens are removed and old and damaged erythrocytes (RBCs) are recycled. The spleen is made up of three regions, namely the marginal zone (MZ), red pulp (RP) and white pulp (WP). Macrophages that reside in the RP are responsible for recycling RBCs as well as the capture and removal of pathogens from the blood. T and B-lymphocytes responsible for the adaptive immune response are mainly localized in the WP. Initiation of an immune response occurs through an encounter of the antigen with MZ macrophages that bridge the RP and the WP. This interface between the immune system and the circulatory system in the spleen provides a perfect environment for the removal of blood-borne pathogens, which are trapped by macrophages in the RP and the MZ. Others have shown that transport of the gram-positive pathogen Listeria monocytogenes (Listeria) from the MZ to the WP is an essential process for the initiation of T-cell mediated adaptive immune responses . Here we investigated whether Salmonella typhimurium (Salmonella), a gram-negative pathogen that has a different life style from Listeria is transported in a similar manner in the spleen. Salmonella and Listeria are intracellular pathogens and are commonly used as models for bacterial infections. After infecting host cells, Listeria escapes from its intracellular vesicle to the host cytoplasm where it replicates. Salmonella, on the other hand, inhabits its Salmonella-containing vacuole (SCV). Listeria initially resides in phagocytes of the MZ and is transported to the WP by CD11c+ dendritic cells (DCs) in less than 2 hours (h) after an intravenous (i.v.) infection . Listeria induces a strong T-cell response, while Salmonella does not. So, we hypothesized that since Salmonella inhabits its SCV, its transport in the spleen will differ from that of Listeria. We found that wild-type Salmonella mainly resides in the MZ and RP regions even after 24h of infection. In contrast, Salmonella mutants, ∆sifA and ∆asd were transported to the splenic WP during the early stages of infection. This suggests a connection between the intracellular lifestyle of bacteria and the capability to initiate adaptive immune response.
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