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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/L64    most recent 90640.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Glasser, S. W. Articles by Korfhagen, T. R. PubMed PubMed Citation Articles by Glasser, S. W. Articles by Korfhagen, T. R.

Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection

¹Division of Pulmonary Biology, ⁴Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, ²Lovelace Respiratory Research Institute, Albuquerque, New Mexico, and ³Medical University of South Carolina, Charleston, South Carolina

Submitted 29 December 2008 ; accepted in final form 16 March 2009

Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV). Pulmonary infection with RSV caused more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc^–/–) mice compared with SP-C replete mice. The RSV-induced pathology resolved more slowly in Sftpc^–/– mice with lung inflammation persistent up to 30 days postinfection. Polymorphonuclear leukocyte and macrophage counts were increased in the bronchoalveolar lavage (BAL) fluid of Sftpc^–/– mice. Viral titers and viral F and G protein mRNA were significantly increased in both Sftpc^–/– and heterozygous Sftpc^+/– mice compared with controls. Expression of Toll-like receptor 3 (TLR3) mRNA was increased in the lungs of Sftpc^–/– mice relative to Sftpc^+/+ mice before and after RSV infection. Consistent with the increased TLR3 expression, BAL inflammatory cells were increased in the Sftpc^–/– mice after exposure to a TLR3-specific ligand, poly(I:C). Preparations of purified SP-C and synthetic phospholipids blocked poly(I:C)-induced TLR3 signaling in vitro. SP-C deficiency increases the severity of RSV-induced pulmonary inflammation through regulation of TLR3 signaling.

interstitial lung disease; Toll-like receptor 3