Interaction of Helicobacter pylori with human myeloid antigen-presenting cells: immunomodulating effects and their dependency on the bacterial cholesterol metabolism

Myeloid APCs are found in the gastric mucosa and most likely involved in H. pylorispecific immune responses. As a result, they are potential targets of bacterial virulence factors that favor immune evasion. In mice, cholesterol-α-glucosyltransferase by H. pylori has previously been shown to mediate immune evasion through interference with APC functions. The aim of this thesis was to investigate, (i) how distinct types of human myeloid APCs interact with H. pylori, (ii) whether H. pylori down-regulates immune functions of these APCs, and (iii) whether such effects depend on the bacterial cholesterol metabolism. To these ends, monocytes were isolated from human peripheral blood and used directly or as progenitors for DCs, classically (M1) and alternatively (M2) activated macrophages. The cells were infected with H. pylori or the isogenic cholesterol- - glucosyltransferase deficient mutant, which is unable to glucosylate cholesterol, and characterized regarding: * phenotypic alterations * phagocytic properties * T-cell stimulation * cytokine secretion This approach enabled to study, in parallel, the outcome of infection with wild type or cholesterol- -glucosyltransferase mutant H. pylori strains in myeloid APCs obtained from single donors, thereby excluding inter-individual differences in comparative assays.