Surfactant Protein-A–Deficient Mice Display an Exaggerated Early Inflammatory Response to a β -Resistant Strain of Influenza A Virus

Publisher Website
Google Scholar
Abstract
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 (LD50) 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-79 Δ 167 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.

This publication has 30 references indexed in Scilit: