Macrophage impairment underlies airway occlusion in primary respiratory syncytial virus bronchiolitis.
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.
Reed
Jennifer L
JL
Respiratory, Inflammation, and Autoimmunity Group, MedImmune, Gaithersburg, Maryland, USA. jennifer.reed@fda.hhs.gov
Brewah
Yambasu A
YA
Delaney
Tracy
T
Welliver
Timothy
T
Burwell
Timothy
T
Benjamin
Ebony
E
Kuta
Ellen
E
Kozhich
Alexander
A
McKinney
LuAnn
L
Suzich
JoAnn
J
Kiener
Peter A
PA
Avendano
Luis
L
Velozo
Luis
L
Humbles
Alison
A
Welliver
Robert C
RC
Coyle
Anthony J
AJ
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
D004002:Clodronic Acid