Pulmonary collectins modulate strain-specific influenza A virus infection and host responses

Samuel Hawgood, Cynthia Brown, Jess Edmondson, Amber Stumbaugh, Lennell Allen, Jon Goerke, Howard Clark, Francis R Poulain

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

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 cytoldne 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.

Original languageEnglish (US)
Pages (from-to)8565-8572
Number of pages8
JournalJournal of Virology
Volume78
Issue number16
DOIs
StatePublished - Aug 2004

ASJC Scopus subject areas

  • Immunology

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