Immunity to Salmonella infection

Sammanfattning: The immune system has several strategies to combat infections. The present study investigates various aspects of the interaction between Gram negative bacteria, particularly Salmonella, and antigen presenting cells (APC). Salmonella is an intracellular bacterium infecting mice and man. Salmonella typhimurium infection in mice is a frequently used model for studying systemic Salmonella infection. One important type of APC is dendritic cells (DC), which initiate and direct immune responses. Bone marrow-derived DC were shown to mature after interacting with Salmonella in vitro. Maturation was detected by upregulation of costimulatory molecules and down modulation of phagocytic ability. Freshly isolated liver DC were shown to have the ability to phagocytose bacteria, present antigens on major histocompatibility complex class I (MHC-I) and MHC-II and produce cytokines upon Salmonella encounter in vitro. In a mouse model for chronic Salmonella infection we found that bacteria persisted for more than 6 months and that these mice had splenomegaly and high serum titers of Salmonella-reactive antibodies. In the spleen and liver of chronically infected mice, a dramatic infiltration of neutrophils was apparent. Moreover, redistribution of macrophages in the liver and DC in the spleen was shown. Bacterial virulence factors are important for Salmonella to infect and survive within host cells. Such a factor is AgfA fimbriae on Salmonella and the similar structure called curli expressed on Escherichia coli. Curli was shown to influence bacterial attachment to, but not internalization by, macrophages. These studies addressing the interaction between Salmonella and APC provide insight into important aspects of immune defense against Salmonella during acute infection, and further increase our understanding of immune parameters when infection is not successfully eradicated.