Abstract
Efferocytosis by alveolar phagocytes (APs) is pivotal in maintenance of lung homeostasis. Increased efferocytosis by APs results in protection against lethal acute lung injury due to pulmonary infections whereas defective efferocytosis by APs results in chronic lung inflammation. In this report, we show that pulmonary delivery of Bacillus Calmette-Guerin (BCG) significantly enhances efferocytosis by APs. Increased efferocytosis by APs maintains lung homeostasis and protects mice against lethal influenza pneumonia. Intranasally treated wild type C57Bl/6 (WT) mice with BCG showed significant increase in APs efferocytosis in vivo compared to their PBS-treated counterparts. All BCG-treated WT mice survived lethal influenza A virus (IAV) infection whereas all PBS-treated mice succumbed. BCG-induced resistance was abrogated by depleting AP prior to IAV infection. BCG treatment increased uptake, and digestion/removal of apoptotic cells by APs. BCG significantly increased the expression of TIM4 on APs and increased expression of Rab5 and Rab7. We demonstrated that increased efferocytosis by APs through pulmonary delivery of BCG initiated rapid clearance of apoptotic cells from the alveolar space, maintained lung homeostasis, reduced inflammation and protected host against lethal IAV pneumonia.
Highlights
Several mechanisms are involved in lung homeostasis such as mucociliary clearance and phagocytosis
CD11c was used in confocal microscopy as a second marker that is widely expressed on mice macrophages, granulocytes, and dendritic cells (DCs) and is an endocytic receptor that in the lung is expressed by alveolar macrophages [20]
alveolar phagocytes (APs) play an important role in reducing inflammation in the lungs by ingestion of apoptotic cells, termed “efferocytosis” [5,17]
Summary
Several mechanisms are involved in lung homeostasis such as mucociliary clearance and phagocytosis. Alveolar phagocytes(APs) consists of mostly alveolar macrophages (AMs), recruited monocytes and dendritic cells (DCs) are the most prominent phagocytes in the lung and play pivotal roles in uptake, digestion and removal of dead and apoptotic cells, cell debris, pathogens and inhaled particles. Defective phagocytosis by APs results in chronic inflammation in the lungs and significantly increases the likelihood of developing chronic obstructive pulmonary disease (COPD), lung injury and cancer [1,2,3,4]. Efferocytosis in the lungs and host defense was no additional external funding received for this study
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