Susceptibility of mice genetically deficient in SP-A or SP-D gene to Invasive Pulmonary Aspergillosis

Madan, Taruna, Reid, Kenneth, Clark, Howard, Singh, Mamta, Nayak, Annapurna, Sarma, P. Usha, Hawgood, Samuel and Kishore, Uday (2010) Susceptibility of mice genetically deficient in SP-A or SP-D gene to Invasive Pulmonary Aspergillosis. Molecular Immunology, 47(10), pp. 1923-1930. ISSN (print) 0161-5890

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Abstract

Pulmonary surfactant proteins, SP-A and SP-D, are carbohydrate pattern recognition molecules of innate immunity, which significantly enhance phagocytosis and killing of Aspergillus fumigatus, a pathogenic fungus, by neutrophils and macrophages. The present study examined the susceptibility of immunosuppressed SP-A gene deficient (SP-A(-/-)) or SP-D gene deficient (SP-D(-/-)) mice to A. fumigatus conidia challenge compared to wild-type (WT) mice. A. fumigatus-challenged SP-A(-/-) (SP-A(-/-) IPA) mice showed less mortality (40%) than the WT-IPA mice (100%) and increased mortality (60%) following administration of SP-A with decreased TNF-alpha and IFN-gamma to IL-4 ratio than SP-A(-/-) IPA mice. The SP-D(-/-) IPA mice (57.14%) showed similar mortality as WT-IPA mice (60%). However, the SP-D (-/-) IPA mice (42.86% mortality on day 2) died earlier than the WT-IPA mice (20% mortality on day 2), showed a higher hyphal density and tissue injury in lungs. Treatment with SP-D or a recombinant fragment of human SP-D rhSP-D reduced the mortality to 50% and 33%, respectively, concomitant with higher IFN-gamma to IL-4 ratios in treated SP-D(-/-) mice, compared to untreated control group. The results showed that SP-D gene deficient mice are more susceptible to IPA while SP-A gene deficient mice acquire resistance to IPA.

Item Type: Article
Additional Information: This work was supported by the Council for Scientific and Industrial Research, the Department of Science and Technology, India, the Medical Research Council, the European Commission and BRIEF.
Research Area: Allied health professions and studies
Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017)
Faculty of Science, Engineering and Computing (until 2017) > School of Life Sciences
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Depositing User: Susan Miles
Date Deposited: 15 Nov 2013 14:54
Last Modified: 15 Nov 2013 14:56
DOI: https://doi.org/10.1016/j.molimm.2010.02.027
URI: http://eprints.kingston.ac.uk/id/eprint/26816

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