The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis

The lung myeloid cell microenvironment comprises airway, alveolar and interstitial macrophages, peripheral blood recruited lung monocytes as well as residential and migratory dendritic cell subsets. Findings from fate mapping, parabiosis, transcriptome and epigenome profiling studies now indicate that tissue macrophage and monocyte subsets possess specialized functions which differentially impact homoeostatic tolerance, pathogen detection and pathogen killing. In the lungs, residential alveolar macrophages are catabolic and immunosuppressive in contrast to the classically pro-inflammatory repertoire of lung monocytes and monocyte-derived dendritic cells recruited during acute inflammation. Here, we review the identity and functions of all lung macrophage and monocyte subsets during homoeostasis and acute lung inflammation, with a special focus on their contributions to influenza virus detection, clearance and the development of influenza-induced lung pathologies. Subsequent implications for the development of new therapeutic targets against influenza-induced lung pathologies will also be discussed.