Cell-type-specific efferocytosis determines functional plasticity of alveolar macrophages

Acid aspiration of gastric contents leads to aspiration pneumonitis, and as such predisposes to severe secondary bacterial infections. Alveolar macrophages are key sentinel cells in the lung, which initiate and resolve an inflammatory process. We found that after acid aspiration resident alveolar macrophages are impaired in their capacity to eliminate the clinically relevant bacterium Pseudomonas aeruginosa ex vivo and in vivo. Reduced bacterial killing peaked around 24 hours after the hit with acid, was detected up to 4 days later, and returned to normal 7 days after acid aspiration. We therefore want to characterize the capacity of avleolar macrophages after acid aspiration over time to respond to Pseudomonas aeruginosa. We expect a pro-resolving M2-like differentiation, which we aim to characterize in more detail: which inflammatory pathways are differentially regulated, are genes associated with bactericidal functions affected, is there a difference in the metabolic response. Two-factorial: infection (uninfected or infected with Pseudomonas aeruginosa) and time (HCl treatment for 0, 1, 4, or 7 days), n=4 in each combination, n = 32 in total from 32 animals.