Surfactant protein-A enhances respiratory syncytial virus clearance in vivo

TLDR

The study aimed to determine the role of surfactant protein‑A (SP‑A) in antiviral host defense against respiratory syncytial virus. The authors generated SP‑A–/– mice and infected them with RSV via intratracheal instillation to assess viral clearance and immune responses. SP‑A deficiency caused increased lung inflammation, higher RSV titers, elevated pro‑inflammatory cytokines, and impaired macrophage oxidant production, whereas exogenous SP‑A administration reduced viral loads and inflammatory cells, confirming SP‑A’s protective role.

Abstract

To determine the role of surfactant protein-A(SP-A) in antiviral host defense, mice lacking SP-A (SP-A–/–) were produced by targeted gene inactivation. SP-A–/– and control mice (SP-A+/+) were infected with respiratory syncytial virus (RSV) by intratracheal instillation. Pulmonary infiltration after infection was more severe in SP-A–/– than in SP-A+/+ mice and was associated with increased RSV plaque-forming units in lung homogenates. Pulmonary infiltration with polymorphonuclear leukocytes was greater in the SP-A–/– mice. Levels of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were enhanced in lungs of SP-A–/– mice. After RSV infection, superoxide and hydrogen peroxide generation was deficient in macrophages from SP-A–/– mice, demonstrating a critical role of SP-A in oxidant production associated with RSV infection. Coadministration of RSV with exogenous SP-A reduced viral titers and inflammatory cells in the lung of SP-A–/– mice. These findings demonstrate that SP-A plays an important host defense role against RSV in vivo.