H Theobald, D A Bejarano, N Katzmarski, J Haub, J Schulte-Schrepping, J Yu, K Bassler, A L Ament, C Osei-Sarpong, F Piattini, L Vornholz, W T'Jonck, A H Györfi, H Hayer, X Yu, S Sheoran, A Al Jawazneh, S Chakarov, K Haendler, G D Brown, D L Williams, L Bosurgi, J H W Distler, F Ginhoux, J Ruland, M D Beyer, M Greter, C C Bain, A I Vazquez-Armendariz, M Kopf, J L Schultze, A Schlitzer
The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal β-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE+ CD11b+ AMs)...
April 26, 2024: Nature Immunology