Alveolar Macrophage ImmuNOmetabolism study

Pneumonia is responsible for an inordinate disease burden worldwide. Alveolar macrophages (AMs) are phagocytes that reside on the surface of the lower respiratory tract, where they represent an initial line of leukocytic antimicrobial defense when pathogens invade the lower airways. AMs showcase an extreme plasticity in immunological functions, which is warranted by their localisation. AMs have the capability to transition from anti-inflammatory housekeeping cells into central nodes of immune activity during lung injury and infection. These functions are relatively well described, however the immunometabolism behind this plasticity remains enigmatic. Which metabolic changes facilitate this adaptive potential is unknown. Can we define specific immunometabolic pathways that drive these unique characteristics, also comparing this to blood-derived macrophages? In addition, we will utilize Optical Coherence Tomography and Confocal Laser Endomicroscopy to in vivo visualize the healthy alveolar compartment and airway wall layers, being the direct boundaries of the microenvironment. This is an observational study in healthy volunteers who undergo a bronchoscopy for bronchoalveolar lavage, biopsies, combined with imaging with OCT/CLE, and phlebotomy.

Alveolar macrophages do not depend on glucose metabolism during infection, but on another metabolic source.

Healthy volunteers will undergo a bronchoscopy at 1 timepoint. At this point, the imaging (OCT and CLE) will be obtained.
The cells obtained from the broncho-alveolar lavage fluid will be used for in vitro studies in which they will be treated/stimulated for 24 hours with different bacterial components mimicing a bacterial infections and with treatments interfering with metabolic pathways.

Bronchoscopy, phlebotomy