The inflammatory chemokine CCL17 is in first line produced by dendritic cells (DCs). As a ligand of CCR4, CCL17 induces chemotaxis, promotes T cell/DC interactions, and influences the migration of DCs. CCL17 has been associated with inflammatory diseases such as contact hypersensitivity (CHS), colitis and atherosclerosis, and CCL17-deficient mice are protected against these diseases. In contrast, the role of CCL17 in infectious diseases is not well understood. Therefore we aim to elucidate the function of CCL17 in the context of infection with the bacterial pathogen, Salmonella Typhimurium (STM).

In the early phase of infection, STM invades the Peyer’s Patches (PP), a site to which CCL17⁺ DC are known to localise. From there it is thought that STM infected DCs migrate to the draining mesenteric lymph nodes (mLN), where they may induce protective immune responses. However Salmonella-infected DCs exhibit altered maturation and decreased viability, rendering it more difficult to ascertain their function during infection. In a mouse model for invasive Salmonellosis, we are studying the influence of CCL17 on the immune responses generated against STM after oral infection. We are analyzing the myeloid cell populations responsible for transporting the bacteria from the gut to the mLN, and specifically exploring the ability of CCL17 to induce activation and migration of Salmonella-infected DCs, and investigate the influence of this chemokine on the antigen-presenting function of infected DCs. Preliminary data from PP and mLN show that monocytes as well as macrophages, but not DCs, harbour STM 3 days post infection. Investigation on the role of CCL17 and in specific of CCL17-expressing DCs in the induction of adaptive immunity to STM should ultimately help us to develop improved vaccination strategies against Salmonellosis in future.