Interstitial Macrophages Mediate Efferocytosis of Alveolar Epithelium During Influenza Infection

Am J Respir Cell Mol Biol. 2024 Jan 11. doi: 10.1165/rcmb.2023-0217MA. Online ahead of print.ABSTRACTEfferocytosis is a process where apoptotic cells are cleared to maintain tissue homeostasis. In the lungs, efferocytosis has been implicated in several acute and chronic inflammatory diseases. A longstanding method to study efferocytosis in vivo is to instill apoptotic cells into the lungs to evaluate macrophage uptake. However, this approach provides non-physiologic levels of cells to the airspaces where there is preferential access to the alveolar macrophages (AMs). To circumvent this limitation, we developed a new method to study efferocytosis of damaged alveolar type 2 (AT2) epithelial cells in vivo. A reporter mouse that expresses TdTomato in alveolar type 2 (AT2) epithelial cells was injured with influenza (strain PR8) to induce apoptosis of AT2 cells. We were able to identify macrophages that acquire red fluorescence after influenza injury indicating efferocytosis of AT2 cells. Furthermore, evaluation of macrophage populations led to the surprising finding that lung interstitial macrophages were the primary efferocyte in vivo. In summary, we present a novel finding that the interstitial macrophage, not the alveolar macrophage, primarily mediates clearance of AT2 cells in the lungs after influenza infection. Our method of studying efferocytosis provides a more physiologic approach in evaluating the spatiotemporal dynamics of apoptotic cell clearance in vivo and opens new...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Source Type: research