Macrophage Impairment Underlies Airway Occlusion in Primary Respiratory Syncytial Virus Bronchiolitis

• Published in: The Journal of infectious diseases Vol. 198; no. 12; pp. 1783 - 1793
• Main Authors: Reed, Jennifer L., Brewah, Yambasu A., Delaney, Tracy, Welliver, Timothy, Burwell, Timothy, Benjamin, Ebony, Kuta, Ellen, Kozhich, Alexander, McKinney, LuAnn, Suzich, JoAnn, Kiener, Peter A., Avendano, Luis, Velozo, Luis, Humbles, Alison, Welliver, Robert C., Coyle, Anthony J.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.12.2008; University of Chicago Press; Oxford University Press
• Subjects: Airway Obstruction - pathology; Airway Obstruction - virology; Alveolar macrophages; Animals; Biological and medical sciences; Bronchiolitis - complications; Clodronic Acid - pharmacology; Epithelial cells; Fundamental and applied biological sciences. Psychology; Human respiratory syncytial virus; Human viral diseases; Humans; Immunity, Innate; Infant, Newborn; Infections; Infectious diseases; Lungs; Macrophages; Macrophages - physiology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred NZB; Microbiology; Respiratory syncytial virus; Respiratory syncytial virus infections; Respiratory Syncytial Virus Infections - complications; Respiratory Syncytial Virus, Human; Respiratory syncytial viruses; T lymphocytes; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Viruses; Infection; Respiratory tract; Microbiology; Respiratory disease; Bronchus disease; Respiratory system; Bronchiolitis; Macrophage
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/593173

Although respiratory syncytial virus (RSV) infection is the most important cause of bronchiolitis in infants, the pathogenesis of RSV disease is poorly described. We studied histopathologic changes in a panel of lung tissue specimens obtained from infants with fatal cases of primary RSV infection. In these tissues, airway occlusion with accumulations of infected, apoptotic cellular debris and serum protein was consistently observed. Similar observations were found after RSV infection in New Zealand black (NZB) mice, which have constitutive deficiencies in macrophage function, but not in BALB/c mice. A deficiency in the number of alveolar macrophages in NZB mice appears to be central to enhanced disease, because depletion of alveolar macrophages in BALB/c mice before RSV exposure resulted in airway occlusion. In mice with insufficient numbers of macrophages, RSV infection yielded an increased viral load and enhanced expression of type I interferon-associated genes at the height of disease. Together, our data suggest that innate, rather than adaptive, immune responses are critical determinants of the severity of RSV bronchiolitis.