Collectin Deficiency in the mouse
Principal Investigator: Sam Hawgood
Abstract: A complex immune system protects the mucosal surfaces of the respiratory tract from the constant exposure to pathogenic microorganisms and environmental allergens. The collectin proteins (collagen-like lectins) are components of this multifaceted system. Two of the 6-member collectin family, surfactant protein A (SP-A) and surfactant protein D (SP-D), are present in the lining fluids of the respiratory tract, in good position to provide immunological surveillance against both microbes and allergens. The long-term objectives behind this proposal are to determine the mechanisms of collectin action in pulmonary host defense and the relative importance of the collectins in maintaining human health. To best focus on specific mechanisms a single model organism, influenza virus (IAV), will be studied in several transgenic mouse models of altered collectin expression. The hypothesis to be tested in this proposal is that SP-A and SP-D limit lung injury from IAV infection by distinct and complementary mechanisms, specifically SP-D acts primarily as a direct viral neutralizing molecule blocking infection of the epithelium while SP-a reduces the viral load primarily by enhancing macrophage phagocytosis. The proposal also tests the idea that the collectins present IAV to the cells of the adaptive immune response and modify the cellular and humoral response to infection. These hypotheses will be tested by four specific aims. Aim 1: To determine the respective role of SP-A and SP-D during strain specific IAV infection in vivo. Aim 2: To characterize the effects of SP-A and SP-D on the response of macrophages to IAV. Aim 3: To determine if SP-A or SP-D influences the humoral and cellular immune response to IAV infection. Aim 4: To characterize the critical functional domains of the collectins in mediating the mouse response to influenza virus. Although our studies are focused on a specific organism, we expect the mechanisms underlying collectin-IAV-host interactions will pertain more generally to the action of collectins in respiratory immune responses.
Funding Period: 1997-07-01 - 2006-06-30
more information: NIH RePORT
- Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generationNades Palaniyar
Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, UK
J Immunol 174:7352-8. 2005..Our findings establish two new roles for these innate immune proteins and that SP-D enhances efficient pinocytosis and phagocytosis of DNA by macrophages and minimizes anti-DNA Ab generation...
- Alveolar surfactant protein D content modulates bleomycin-induced lung injuryJohn Casey
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania School of Medicine, and Division of Neonatology, Children s Hospital of Philadelphia 19104, USA
Am J Respir Crit Care Med 172:869-77. 2005..Surfactant protein D (SP-D) is a collectin family member with demonstrated immunomodulatory properties in vitro. We hypothesized that SP-D modulates inflammation during noninfectious lung injury in vivo...
- Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient miceAnja Jung
Department of Anatomy, Division of Electron Microscopy, University of Gottingen, Gottingen, Germany
Anat Rec A Discov Mol Cell Evol Biol 286:885-90. 2005..The design-based stereological approach presented here provides a framework for the quantitative lung structure analysis in gene-manipulated mice as well as in human lung disease...
- Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas aeruginosaEric Giannoni
Department of Pediatrics, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143 0110, USA
Am J Respir Cell Mol Biol 34:704-10. 2006..aeruginosa by stimulating phagocytosis by alveolar macrophages and by modulating the inflammatory response in the lungs. These findings also show that the functions of SP-A and SP-D are not completely redundant in vivo...
- N-linked glycosylation attenuates H3N2 influenza virusesDavid J Vigerust
St Jude Children s Research Hospital, 332 N Lauderdale Street, Memphis, TN 38105 2794, USA
J Virol 81:8593-600. 2007..The continued exploration of interactions between highly glycosylated viruses and surfactant proteins may lead to an improved understanding of the biology within the lung and strategies for viral control...
- Expression of surfactant protein D in human corneal epithelial cells is upregulated by Pseudomonas aeruginosaMinjian Ni
School of Optometry, University of California, Berkeley, CA 94720, USA
FEMS Immunol Med Microbiol 54:177-84. 2008..aeruginosa or its antigens, they can involve different regions of the same ligand. The data suggest that separate mechanisms may regulate SP-D secretion and production by human corneal epithelia...
- Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein D and is compromised by bacterial elastase in a murine null-infection modelJames J Mun
School of Optometry, University of California, Berkeley, CA 94720 2020, USA
Infect Immun 77:2392-8. 2009..aeruginosa from the healthy ocular surface and that proteases can compromise that clearance. The data also suggest that SP-D degradation in vivo is a mechanism by which P. aeruginosa proteases could contribute to virulence...