Graduate Student Boston Univ. Chobanian & Avedisian Sch. of Med., United States
Disclosure(s):
Elise Armstrong, MS: No financial relationships to disclose
Introduction/Rationale: Innate immune memory of lung macrophages is a crucial host safeguard against repeated respiratory infections. Based on the tissue compartments, there are alveolar macrophages and interstitial macrophages (IMs). IMs are further subdivided into CD206- and CD206+ subpopulations that have distinct localizations, transcriptomes, and functions. Whether IM subpopulations have the capacity to remodel after repeated infections is unknown.
Methods: Ontogeny of IMs was determined using Flk/switch reporter mice, whereby embryonic cells express tdTomato and bone marrow derived cells express GFP. Mice had left lobe intratracheal instillations of pneumococcus (“Experienced”) or saline (“Naïve”) at days 0 and 7. At day 35, IMs were studied using flow cytometry. Differences in localization were determined through mfIHC in Cx3cr1+/GFP reporter mice. IM recruitment was tested in B- and T-cell depleted mice (using cell-depleting antibodies against CD20 and CD4, respectively) and CCR2-/- mice. Transcriptomic analysis of lung macrophages was carried out by CITE scRNA-sequencing using surface protein markers to differentiate IM subsets. Phagocytic activity of IMs was determined by instilling fluorescent pneumococcus or E. coli
Results: The majority of IMs in the naïve lung are primarily bone marrow derived. Following repeated pneumococcus infections, both CD206- and CD206+ IMs were more abundant in experienced lungs compared to naïve lungs. Immunohistological staining showed IMs become the predominant lung macrophage in experienced mice. CD206+ IM recruitment was dependent on a second infection, and independent of B and T lymphocytes as well as CCR2. Only CD206+ IMs showed remodeled surface marker expression, transcriptome, and phagocytic capacity.
Conclusion: CD206+ IMs are phenotypically and functionally remolded after infection. Future mechanistic studies will evaluate how the enhanced phagocytic phenotype impacts host defense.
