Pleural macrophages translocate to the lung during infection to promote improved influenza outcomes

Abstract

ABSTRACT Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 to 500,000 deaths annually. Macrophages have been implicated in both the resolution and progression of the disease, but the drivers of these outcomes are poorly understood. We probed mouse lung transcriptomic datasets using the Digital Cell Quantifier algorithm to predict immune cell subsets that correlated with mild or severe influenza A virus (IAV) infection outcomes. We identified a novel lung macrophage population that transcriptionally resembled small serosal cavity macrophages and correlated with mild disease. Until now, the study of serosal macrophage translocation in the context of infections has been neglected. Here, we show that pleural macrophages (PMs) migrate from the pleural cavity to the lung after infection with pH1N1 A/California/04/2009 IAV. We found that the depletion of PMs increased morbidity and pulmonary inflammation. There were increased proinflammatory cytokines in the pleural cavity and an influx of neutrophils within the lung. Our results show PMs are recruited to the lung during IAV infection and contribute to recovery from influenza. This study expands our knowledge of PM plasticity and provides a new source of lung macrophages independent of monocyte recruitment and local proliferation. GRAPHICAL ABSTRACT