Development of a polymicrobial model system for mechanistic research of upper respiratory tract host-microbe interactions

The upper respiratory tract (URT), and in particular the sinonasal cavities, are constantly exposed to the external environment and its allergens and infectious agents. The epithelium, the tissue lining the sinonasal cavities, is colonised by a microbial community that aids in structural development of the epithelium and immune priming, and acts as colonisation barrier towards incoming pathogens. Furthermore, the resident bacterial community can play a role in disease development and persistence, e.g. in chronic rhinosinusitis. Chronic rhinosinusitis is a chronic inflammation of the epithelium of the nose and sinuses that affects 11 % of the adult population in Europe and results in reduced quality of life and an economic burden. The importance of the sinonasal microbiota in this disease is recognised, yet in vitro models of the URT that are used to study and test e.g. drugs, pathogens, and live biotherapeutic products in the context of this disease, generally do not include a representative microbial community. In this PhD research, a model system of the human URT was developed that incorporates the epithelium, an immune component, and donor-derived nasal microbiota. We observed that inclusion of an immune component could steer the microbial community, and that different inflammatory states affected the host response towards nasal microbiota from healthy individuals. In view of probiotic treatment strategies for upper airway diseases, host-microbe interactions with Lacticaseibacillus casei AMBR2 were examined in the complex microbial background of the model system. Finally, making the model system more physiologically representative, the co-culture system was translated to a microfluidic setup, the human-microbial crosstalk (HuMiX) device.