The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation

Grabiec, Aleksander M.; Hussell, Tracy

Taken together, these studies suggest that efferocytosis is not only a constitutive function of macrophages required for maintaining immune homeostasis in health and during inflammatory response but also an important antimicrobial effector mechanism. However, it has to be noted that apart from bactericidal activity against specific pathogens, the antiinflammatory signal associated with apoptotic cell uptake by phagocytes might prevent the mounting of an efficient immune response in the context of other lung infections. Prior exposure of mouse airway macrophages to apoptotic cells results in suppression of FcR-mediated phagocytosis and killing of bacteria, and intrapulmonary administration of apoptotic cells causes significant impairment of S. pneumoniae clearance from the infected lung [56] . Suppression of antimicrobial responses of airway macrophages is also augmented by glucocorticoids, which promote efferocytosis, and treatment of mice with apoptotic cells in the presence of glucocorticoids is associated with elevated bacterial burden in the lungs [126] . Even though validation of these observations in human systems is necessary, they clearly indicate that efferocytosis plays a dual role in lung infections: while efficient apoptotic cell uptake is required for resolution of the inflammatory response and elimination of certain intracellular pathogens, the antiinflammatory programmes activated upon prolonged exposure to apoptotic cells might increase susceptibility to secondary infections and infection-related exacerbations of chronic inflammatory lung diseases.