Contact-dependent immune response by macrophages

Abstract

Infections caused by Aspergillus fumigatus are a significant cause of death in immune-compromised humans. Alveolar macrophages (AM) comprise an important line of immune defense in the lung and help prevent infections resulting from inhalation of A. fumigatus conidia. Despite significant study in this area, details about how AM engage A. fumigatus are not completely understood. A better description about how A. fumigatus conidia are phagocytosed by AM is needed to better understand the innate resistance of healthy individuals to various airborne infections. The focus of this study was to determine whether the ability of AM to phagocytose A. fumigatus conidia is dependent upon attachment to a surface. We began by showing that AM supported on the epithelial cells in the alveolar space of the lung phagocytose conidia. We next compared phagocytosis of A. fumigatus conidia in tissue culture macrophages bound on a plastic substrate to that of macrophages when free in solution. Our results show a loss of phagocytosis by macrophages when detached from a physical support. Monocyte-derived macrophages show a corresponding contact-dependent production of microbicidal reactive oxygen species (ROS), known to be crucial in the resistance to A. fumigatus infections within the lungs. Our results suggest macrophages require physical contact with a surface to efficiently phagocytose A. fumigatus conidia. Further studies in this area may help provide a better understanding of the inflammatory response of AM that could be used to enhance defense mechanisms in humans at risk of infection