Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection.
Mice lacking surfactant protein SP-A [SP-A(-/-)] and wild type SP-A(+/+) mice were infected with influenza A virus (IAV) by intranasal instillation. Decreased clearance of IAV was observed in SP-A(-/-) mice and was associated with increased pulmonary inflammation. Treatment of SP-A(-/-) mice with exogenous SP-A enhanced viral clearance and decreased lung inflammation. Uptake of IAV by alveolar macrophages was similar in SP-A(-/-) and SP-A(+/+) mice. Myeloperoxidase activity was reduced in isolated bronchoalveolar lavage neutrophils from SP-A(-/-) mice. B lymphocytes and activated T lymphocytes were increased in the lung and spleen, whereas T helper (Th) 1 responses were increased [interferon-gamma, interleukin (IL)-2, and IgG(2a)] and Th2 responses were decreased (IL-4, and IL-10, and IgG(1)) in the lungs of SP-A(-/-) mice 7 days after IAV infection. In the absence of SP-A, impaired viral clearance was associated with increased lung inflammation, decreased neutrophil myeloperoxidase activity, and increased Th1 responses. Because the airway is the usual portal of entry for IAV and other respiratory pathogens, SP-A is likely to play a role in innate defense and adaptive immune responses to IAV.
LeVine
Ann Marie
AM
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. levia@chmcc.org
Hartshorn
Kevan
K
Elliott
James
J
Whitsett
Jeffrey
J
Korfhagen
Thomas
T
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006384:Hemagglutination / Q000187:drug effects; D007136:Immunoglobulins / Q000097:blood; D029521:Alphainfluenzavirus / Q000187:drug effects / Q000472:pathogenicity; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008171:Lung Diseases / Q000473:pathology / Q000503:physiopathology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D011510:Proteolipids / Q000235:genetics / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000473:pathology; D019562:Viral Load
D016207:Cytokines; D007136:Immunoglobulins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D009195:Peroxidase