Role of Innate lymphoid cells (ILC) and aryl hydrocarbon receptor (AhR) during pulmonary bacterial infections
Pulmonary diseases by Mycobacterium species and Pseudomonas aeruginosa (P.aer) represent one major cause of hospitalization and mortality, the latter especially in immunocompromised individuals and in patients affected by cystic fibrosis (CF). IL-17 and IL-22 responses are important for the resistance against P.aer, while likely dispensable in primary immunity to Mycobacterium tuberculosis (M.tb). However, deficiency of RORgt leads to higher susceptibility to mycobacterial diseases both in humans and mice. Innate lymphoid cell (ILC), in particular RORgt+ ILC3, and in some cases ILC2, can produce IL-17 and IL-22; however, the roles of ILC3 or of other ILC subsets during P.aer or M.tb infection remain unclear.
We have recently identified the aryl hydrocarbon receptor (AhR) as a pathogen recognition receptor and new important pathway for the resistance against M.tb and P.aer infection. However, we have only started to elucidate the immunological mechanisms responsible for this effect. Among lymphocytes, AhR is expressed by Th17 cells as well as by different ILC subsets, especially ILC3, and is crucial to maintain the ILC3 pool as well as their IL-22 production.
Based on these findings, we want to test the hypothesis whether ILC3 or other ILC subsets contribute to the immune response against M.tb and P.aer pulmonary infection and whether they can modulate bacterial dissemination and tissue damage response in an AhR-dependent manner. These questions will be addressed in vitro and in vivo using experimental infection models of M.tb and P.aer as well as ex vivo in patient samples.
This project will enable us to understand the role of ILCs in the defence against pulmonary bacterial infections and to possibly open new avenues of intervention, for their prevention and treatment.