The lung is the central organ for the exchange of gas in the human body. It is characterized by a large surface area in relation to its volume and comprises the distal branching of the trachea, bronchial tubes, bronchioles and alveoli.
The liver harbors about 80% of all macrophages of the human body. Circulating monocytes are constantly patrolling within the hepatic vascular system in search of pathogen-associated molecular substances and are able to migrate into the hepatic tissue after detection of pathogens. To avoid unwanted immune responses under physiological conditions endogenous microbial molecules derived from commensal microbiota are well tolerated by the liver. However, in case of blood borne infections a prompt and robust inflammatory response is required to prevent further dissemination of the pathogen. In this context Kupffer cells, tissue resident macrophages of the liver, are central players in orchestrating a balanced immune response between immunotolerance and inflammation.
In the gut commensal microorganisms of the intestinal microbiome support the digestion and absorption of nutrition by the gut. Microbial colonization is supported by the host via a mucus layer secreted by epithelial cells organized in a complex tissue comprising villi and crypts that form a tight and protective barrier between the microbiota and the circulation. A physiological communication between the members of the intestinal microbiome and their host is crucial for the maintenance of homeostasis in the human body. Thus, deregulation and imbalance of these interactions known as dysbiosis are directly associated with the development of human diseases, including diabetes, obesity, inflammatory bowel disease (IBD), cancer, depression and non-infectious inflammatory diseases caused by opportunistic pathogens.
To create a platform for the investigation of the underlying mechanisms of dysbiosis associated diseases, we established a three-dimensional microphysiological model of the human intestine. This model resembles organotypic microanatomical structures and includes tissue resident innate immune cells exhibiting features of mucosal macrophages and dendritic cells. The model displays the physiological immune tolerance of the intestinal lumen to microbial-associated molecular patterns and can, therefore, be colonised with live microorganisms. It represents a valuable tool to systematically explore the underlying mechanisms of microbial communication, host-microbe interactions, microbial pathogenicity mechanisms, and immune cell activation under physiologically relevant conditions in vitro. Further, it allows the screening and development of novel treatment strategies for IBD including pharmaceutical treatments and adjustment of dysbiosis conditions to maintain physiological conditions of the human microbiota that keep opportunistic pathogens in their commensal state and prevents the onset of related inflammatory diseases.