Dendritic cells: sensors of extreme antigen dilutions and role in immunity against Salmonella typhimurium infections

Abstract

The intention of the work described in this thesis was to identify whether extremely high dilutions of antigen can induce changes in dendritic cell maturation and dendritic cell ability to initiate immune responses. Basic research performed trying to address whether such ultra-high, homeopathic, dilutions of antigen have a biological role is limited, while clinical investigations into this matter are inconclusive. Homeopathy is, however, gaining popularity, and is very often at the epicentre of intense scientific and medical debate. We hypothesised that dendritic cells, being an excellent APC, might be a good candidate cell to investigate this controversial topic. While dendritic cells are excellent APCs, capable of inducing T cell responses 100 times more effectively than other lymphocytes, there is mounting evidence suggesting that they might also be involved in bacterial dissemination during Salmonella infections. We investigated the role of dendritic cells in the development of protective immune responses against Salmonella typhimurium infections. Furthermore, we assessed whether the APC derived cytokine, IL-23, which shares the common p40 subunit with IL-12 p70, is required for the development of primary, memory as well as protective immune responses against Salmonella typhimurium. While IL- 23 has been shown to be important for the maintenance of IL-17 responses by T cells, its role during Salmonella induced pathology remains elusive. Our work identified some interesting aspects of this cytokine in immunity against Salmonella typhimurium infections.