The defective function of gut dendritic cells of rats with cirrhosis and bacterial translocation is corrected by bowel decontamination with antibiotics

Resumen

Introduction: Gut bacterial translocation (GBT) of enteric gramnegative bacteria to mesenteric lymph nodes (MLN) is a key event in the pathogenesis of bacterial infections in cirrhosis. Passage of intestinal microorganisms to the circulation is safeguarded by gut lymphoid tissue, in which dendritic cells (DC) play an essential function. DC phagocyte antigens from the intestinal lumen and transport them to the MLN, where they initiate specific immune responses. Aims: To investigate in rats with CCl4-cirrhosis: i. the activation state, and capacity to phagocyte and migrate of DC of MLN and intestinal lamina propria, and ii. the relationship of the abnormalities with GBT to MLN. Methods: DC (OX62+RT1BC+D45RA-CD3-) from MLN and intestinal lamina propria of CCl4-cirrhosis and control rats were identified by flow cytometry. In vitro functional studies included the ability of DC to phagocyte latex particles and to migrate to CCL21 using transwell. GBT was defined by MLN culture positivity. Bacterial DNA was also identified in MLN. Results: (mean±SD) Compared with controls, MLN-DC of cirrhotic rats without GBT had greater (p<0.05) frequency (0.7±0.3 vs. 0.4±0.1%), expression of class II-MHC (939±312 vs. 554±152 mean f luorescence intensity), frequency of the proinflammatory CD4+ subset (65.7±7vs.57.1±11%), phagocytic activity (29.7±7 vs. 22.5±4 %) and migration ability (14.4±3 vs. 6.5±1.8%). 85% of these rats had bacterial DNA in MLN. In contrast and compared with controls, MLN-DC of rats with GBT (54%) had similar frequency and migration ability (14.7±3%), but lowered (p<0.05) expression of class II-MHC (454±68 mean fluorescence intensity), frequency of CD4+ subset (44±8.1%), and phagocytic activity (14.7±3%). Bowel decontamination with antibiotics reduced GBT to 8%, and normalized the frequency, class II-MHC expression, and phagocytic and migration capacities of MLN DC. Lamina propria DCs of cirrhotic rats had similar behavior. Conclusions: The enteric bacterial pressure stimulates migration andphagocytosis of intestinal DC of cirrhotic rats. Cirrhotic rats with GBT show an impaired function of intestinal DC, which is corrected by bowel decontamination. The latter suggests that damage of intestinal (lamina propria and MLN) DC in cirrhosis could be the result of an overwhelmed immune system, and not intrinsically due to the liver disease. (Resumen completo publicado en: The 45th annual meeting of the European Association for the Study of the Liver (EASL). Abstracts of the International Liver Congress™ 2010. J Hepatol 2010;52:S212.)