7th Annual BMRP Investigator Meeting - Abstract

Neil Rayment^b, Barry Hudspith and Jeremy Sanderson^a

 

Nutritional Sciences Division, King’s College Hospital (London, England)

 

Intestinal macrophages are important in the regulation of gut homeostasis. We and others have reported the persistence of strains of E. coli in lamina propria macrophages in patients with Crohn’s disease (CD). These macrophages appear unable to complete the normal lysosomal process of bacterial killing and therefore viable (culturable) bacteria persist within these cells.We used laser capture micro-dissection (LCM) to investigate differences in the cytokine profile of bacteria laden and bacteria free macrophages isolated from CD patients with specific known genotypes (NOD2/CARD15, ATG16LI and IRGM)and compared these to intestinal macrophages isolated from control patients. In addition we measured the cytokine response of autologous peripheral blood monocytes (PBM’s) and their derived macrophages to specific E. coli strains. Preliminary LCM analysis shows down-regulated expression of IL-1, MHC II, and iNOS in E.coli containing macrophages compared to those free of bacteria and controls. When comparing PBM’s from CD patients and controls, four E. coli isolates stimulated similar production of the cytokines IL-8 and IL-10 but less IL-23 and TNFα. The reduction in TNFα was significant (p = 0.01) and correlated with presence of the CD related polymorphism ATG16LI. These data suggest that host factors may be an important factor in determining the persistence of bacteria in macrophages in CD and are likely to contribute to disease pathogenesis.  

  

^aPrincipal Investigator; ^bCo-investigator and Presenter