Innate imprinting of resident alveolar macrophages by a preceding allergic bronchial inflammation increases the inflammatory reactivity through autocrine IFN-β. (141.18)

Abstract

Abstract Macrophages play an important and dynamic role in the initiation, propagation and resolution of inflammation. We investigated the dynamics of resident alveolar macrophages (rAM) and its pathophysiological consequences in experimental asthma. Using CD45 chimeric mice and intratracheal instilled fluorescent microparticles to distinguish resident from elicited AM, we observed a near complete disappearance of rAM during consecutive allergen challenges. As a consequence, after clearance of inflammation, inflammation-experienced rAM replaced the initial population of rAM. Strikingly, these secondary rAM showed a markedly altered responsiveness to LPS stimulation. Especially genes induced by IFN-β showed strongly increased expression in secondary rAM as opposed to their near absent induction in primary rAM. This switch from an IFN-β deficient to an IFN-β adequate phenotype increased the inflammatory sensitivity of secondary rAM as observed with rAM from IFN-β -/- mice. Also the basal differentiation status of secondary rAM was modified, dependent on the nature of the preceding allergic inflammation. M2-biased differentiation was seen following eosinophilic asthma while M1-biased differentiation was present following neutrophilic hypersensitivity pneumonitis. Taken together, these observations indicate innate imprinting of rAM by preceding allergic inflammation in the lungs.