Infection history and cellular origin shape long-term alveolar macrophage reprogramming 2301676

作者：Lucia Rodriguez, Olivier Botman, Abdulkader Azouz, Mickaël Dourcy, Daniel Wendisch, Rebekah Crake, Justine Javaux, R Sandor, Thomas Marichal, Florent Ginhoux, Stanislas Goriely, Laurent Gillet, Bénédicte Machiels · 发表于：The Journal of Immunology · 年份：2026 · DOI：10.1093/jimmun/vkag141.1230 · 研究领域：Immune cells in cancer、interferon and immune responses、Epigenetics and DNA Methylation

Abstract Introduction Alveolar macrophages (AMs) are essential sentinels of the lung, maintaining alveolar homeostasis through surfactant clearance, pathogen removal, and regulation of inflammation and tissue repair. During viral infection, circulating monocytes are recruited to the lung and may give rise to monocyte-derived AMs (Mo-AMs). Whether long-term differences between resident and Mo-AMs reflect intrinsic ontogeny or virus-specific imprinting remains unclear. Methods We integrated monocyte fate mapping with phenotypic, transcriptomic, and epigenetic profiling to delineate the relative contributions of cellular origin and virus-specific imprinting on AMs following infection with DNA (Murid herpesvirus 4, MuHV-4; Mouse adenovirus 1, MAV-1) and RNA (Influenza A virus PR8; Pneumonia virus of mice, PVM) viruses. Results Our results show that Mo-AMs emerge and persist long-term in a virus-specific proportion, with monocyte contribution to the AM compartment increasing over time. By 60 days post-infection, Mo-AMs acquire a transcriptomic profile broadly similar to resident AMs but retain enhanced expression of gene programs associated with fibrosis, activation, and metabolic reprogramming, while sustaining reduced expression of canonical resident AM markers. Transcriptomic profiling further revealed that infiltrating monocytes and repair-phase macrophages display virus-specific signatures, with subsets of these programs maintained long-term in AMs. MuHV-4 and MAV-1 infection...