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- Title
Monocyte-derived alveolar macrophages autonomously determine severe outcome of respiratory viral infection.
- Authors
Li, Fengqi; Piattini, Federica; Pohlmeier, Lea; Feng, Qian; Rehrauer, Hubert; Kopf, Manfred
- Abstract
Various lung insults can result in replacement of resident alveolar macrophages (AM) by bone marrow monocyte–derived (BMo)–AM. However, the dynamics of this process and its long-term consequences for respiratory viral infections remain unclear. Using several mouse models and a marker to unambiguously track fetal monocyte–derived (FeMo)–AM and BMo-AM, we established the kinetics and extent of replenishment and their function to recurrent influenza A virus (IAV) infection. A massive loss of FeMo-AM resulted in rapid replenishment by self-renewal of survivors, followed by the generation of BMo-AM. BMo-AM progressively outcompeted FeMo-AM over several months, and this was due to their increased glycolytic and proliferative capacity. The presence of both naïve and experienced BMo-AM conferred severe pathology to IAV infection, which was associated with a proinflammatory phenotype. Furthermore, upon aging of naïve mice, FeMo-AM were gradually replaced by BMo-AM, which contributed to IAV disease severity in a cell-autonomous manner. Together, our results suggest that the origin rather than training of AM determines long-term function to respiratory viral infection and provide an explanation for the increased severity of infection seen in the elderly. Nature over nurture: Alveolar macrophages derived from fetal monocytes (FeMo-AM) are crucial for defense against respiratory viral infections. During influenza A virus (IAV) infection, FeMo-AM are depleted, but it is unclear whether this population is replenished by self-renewing FeMo-AM or by infiltration of bone marrow–derived (BMo)–AM. Li et al. used multiple mouse models to investigate the long-term phenotype, fate, and function of FeMo-AM and BMo-AM after recurrent influenza A virus infection. AM were initially replaced by self-renewal of FeMo-AM but, over time, were outcompeted by BMo-AM, which had superior glycolytic and proliferative capacity. Replacement of FeMo-AM by naïve, inflammation-experienced, or aged BMo-AM promoted IAV pathogenesis and mortality. These findings demonstrate that the origin of the AM rather than previous experience defined their long-term function in recurrent viral infection.
- Subjects
VIRUS diseases; ALVEOLAR macrophages; RESPIRATORY infections; INFLUENZA; INFLUENZA A virus; BONE marrow
- Publication
Science Immunology, 2022, Vol 7, Issue 73, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abj5761