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
Subject
Host defense
Immunology
Aspergillus
Alveolar macrophage