title: Macrophage impairment underlies airway occlusion in primary respiratory syncytial virus bronchiolitis.
abstract: 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.
authors.affiliation: Respiratory, Inflammation, and Autoimmunity Group, MedImmune, Gaithersburg, Maryland, USA. jennifer.reed@fda.hhs.gov
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reed
authors.forename: Yambasu A
authors.initials: YA
authors.lastname: Brewah
authors.forename: Tracy
authors.initials: T
authors.lastname: Delaney
authors.forename: Timothy
authors.initials: T
authors.lastname: Welliver
authors.forename: Timothy
authors.initials: T
authors.lastname: Burwell
authors.forename: Ebony
authors.initials: E
authors.lastname: Benjamin
authors.forename: Ellen
authors.initials: E
authors.lastname: Kuta
authors.forename: Alexander
authors.initials: A
authors.lastname: Kozhich
authors.forename: LuAnn
authors.initials: L
authors.lastname: McKinney
authors.forename: JoAnn
authors.initials: J
authors.lastname: Suzich
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kiener
authors.forename: Luis
authors.initials: L
authors.lastname: Avendano
authors.forename: Luis
authors.initials: L
authors.lastname: Velozo
authors.forename: Alison
authors.initials: A
authors.lastname: Humbles
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welliver
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
mesh_terms: D000402:Airway Obstruction / Q000473:pathology* / Q000821:virology*; D000818:Animals; D001988:Bronchiolitis / Q000150:complications*; D004002:Clodronic Acid / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D018357:Respiratory Syncytial Virus Infections / Q000150:complications*; D018113:Respiratory Syncytial Virus, Human
chemical_list: D004002:Clodronic Acid