Pulmonary collectins modulate strain-specific influenza a virus infection and host responses.
Collectins are secreted collagen-like lectins that bind, agglutinate, and neutralize influenza A virus (IAV) in vitro. Surfactant proteins A and D (SP-A and SP-D) are collectins expressed in the airway and alveolar epithelium and could have a role in the regulation of IAV infection in vivo. Previous studies have shown that binding of SP-D to IAV is dependent on the glycosylation of specific sites on the HA1 domain of hemagglutinin on the surface of IAV, while the binding of SP-A to the HA1 domain is dependent on the glycosylation of the carbohydrate recognition domain of SP-A. Here, using SP-A and SP-D gene-targeted mice on a common C57BL6 background, we report that viral replication and the host response as measured by weight loss, neutrophil influx into the lung, and local cytokine release are regulated by SP-D but not SP-A when the IAV is glycosylated at a specific site (N165) on the HA1 domain. SP-D does not protect against IAV infection with a strain lacking glycosylation at N165. With the exception of a small difference on day 2 after infection with X-79, we did not find any significant difference in viral load in SP-A(-/-) mice with either IAV strain, although small differences in the cytokine responses to IAV were detected in SP-A(-/-) mice. Mice deficient in both SP-A and SP-D responded to IAV similarly to mice deficient in SP-D alone. Since most strains of IAV currently circulating are glycosylated at N165, SP-D may play a role in protection from IAV infection.
University of California-San Francisco, Laurel Heights Campus, 3333 California St., Suite 150, San Francisco, CA 94118-1944, USA. Hawgood@itsa.ucsf.edu
Samuel
S
Hawgood
Cynthia
C
Brown
Jess
J
Edmondson
Amber
A
Stumbaugh
Lennell
L
Allen
Jon
J
Goerke
Howard
H
Clark
Francis
F
Poulain
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D009504:Neutrophils / Q000276:immunology; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014774:Virulence
D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D