Surfactant protein-A--deficient mice display an exaggerated early inflammatory response to a beta-resistant strain of influenza A virus.
Surfactant protein (SP)-A is a member of the collectin family of proteins. In vitro, SP-A binds influenza A virus (IAV), neutralizes infectivity, and enhances uptake by macrophages. SP-D also binds and neutralizes certain strains of IAV. To determine if SP-A has a role in protecting the intact animal against IAV infection, we inoculated gene-targeted SP-A-deficient mice (-/-) and littermate controls (+/+) with either saline or increasing doses of an IAV strain that binds SP-A but not SP-D. IAV was more virulent in SP-A-/- compared with +/+ mice, with a significantly lower mean lethal dose (LD(50)) and significantly greater weight loss during infection. SP-A-/- mice also had increased airway epithelial injury and more alveolar cellular infiltrates than +/+ mice. On Day 2, SP-A-/- mice had more neutrophils and higher MIP-2 levels in the lung than +/+ mice. We conclude the altered host response and increased susceptibility to X-79Delta167 infection in SP-A-/- mice reflects a protective role for SP-A in regulating the host response to IAV. Because the recovery of virus from lung homogenates on Days 2 and 6 after inoculation was comparable in -/- and +/+ mice, we speculate SP-A reduces IAV virulence independently of direct viral neutralization.
Li
Gordon
G
Department of Pediatrics and Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94118-1245, USA.
Siddiqui
Jiyauddin
J
Hendry
Michael
M
Akiyama
Jennifer
J
Edmondson
Jess
J
Brown
Cynthia
C
Allen
Lennell
L
Levitt
Stacey
S
Poulain
Francis
F
Hawgood
Samuel
S
D000818:Animals; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000821:virology; D009980:Influenza A virus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D011510:Proteolipids / Q000276:immunology; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000172:deficiency* / Q000276:immunology; D014774:Virulence
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants