The gut digests, absorbs and metabolises nutrients whilst also acting as a barrier to pathogens entering from the intestinal lumen. Not all intestinal microbes are harmful and the full development of the gut immune system is shaped by interactions with commensal bacteria in a complex interplay which allows responses to harmless bacteria and nutrients to be suppressed whilst developing protective immune response against pathogens. 1 2 Most of these responses occur in the intestinal mucosa and underlying lamina propria; however, transport of nutrients or translocation of pathogens into the portal circulation means that a second level of protection is required in the liver to respond to antigens that evade the gut immune system. 3 In addition, pathogens can enter the liver directly via the systemic circulation or from the gut lumen via the biliary epithelium. Immune responses in the gut and to a lesser extent liver are well-described but the mechanisms that control immunological cross-talk between these two linked sites are only beginning to be elucidated. 4 They provide insights into the pathogenesis of diseases that affect both sites including infections and inflammatory bowel disease (IBD).