Cigarette smoking worsens Crohn’s disease (CD) but little is known regarding the mechanisms. Aberrant dendritic cell (DC) recognition and presentation of bacterial antigens may contribute to inflammatory bowel disease (IBD) pathogenesis. We reported that in vitro cigarette smoke extract (CSE) exposure of monocyte-derived DC (MoDC) prior to stimulation of autologous T cells resulted in Th1 skewing in CD samples, however, how this may impact bacterial-DC interactions ans subsequent T cell polarization remains unclear. We hypothesize that CSE alters DC responses upon bacterial infection in CD patients compared to healthy control (HC). T-cell profiles were used to assess DC responses to in vitro salmonella infection following CSE exposure.
Methods
Mo-DC were differentiated from peripheral blood of CD (n=13) and HC (n=16) using IL-4/GM-CSF and exposed to freshly prepared CSE for 24 hours, followed by infection with salmonella Typhimurium for 24 hours. The infected Mo-DC were co-cultured with autologous T-cells for an additional 7-days and T-cell activation assessed using FACS.
Results and conclusions
CSE exposure to Mo-DC significantly reduced salmonella-specific Th1 cell polarization in HC samples, but this was not seen in CD samples (Fig.A), leading to CSE-driven changes between the two cohorts were statistically significant (Fig.B). Therefore CSE differentially influences polarization of IFN-gamma secreting Th1 cells by DC in CD patients compared to HC.