Susceptibility of mice genetically deficient in SP-A or SP-D gene to invasive pulmonary aspergillosis
Susceptibility of mice genetically deficient in SP-A or SP-D gene to invasive pulmonary aspergillosis
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.
fungal, infection, gene deficient mice, lung, surfactant protein, a fumigatus
1923-1930
Madan, Taruna
578d2149-4657-4415-8348-f5ced1792a9f
Reid, Kenneth B.M.
74c6c3e3-d682-446d-b159-b635e6056e4e
Clark, Howard
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Singh, Mamta
8045ff40-6eb4-41dc-96f3-e958beabe784
Nayak, Annapurna
8b407c7d-9724-46e4-8f2a-acdfc409098b
Sarma, P. Usha
4112a632-b2c1-40d8-939f-6ab5c31f9b19
Hawgood, Samuel
5e406d87-8445-448a-a068-b693d061d6dd
Kishore, Uday
955fd14f-7418-49d2-8b71-f3fe1f791e8e
June 2010
Madan, Taruna
578d2149-4657-4415-8348-f5ced1792a9f
Reid, Kenneth B.M.
74c6c3e3-d682-446d-b159-b635e6056e4e
Clark, Howard
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Singh, Mamta
8045ff40-6eb4-41dc-96f3-e958beabe784
Nayak, Annapurna
8b407c7d-9724-46e4-8f2a-acdfc409098b
Sarma, P. Usha
4112a632-b2c1-40d8-939f-6ab5c31f9b19
Hawgood, Samuel
5e406d87-8445-448a-a068-b693d061d6dd
Kishore, Uday
955fd14f-7418-49d2-8b71-f3fe1f791e8e
Madan, Taruna, Reid, Kenneth B.M., 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), .
(doi:10.1016/j.molimm.2010.02.027).
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.
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Published date: June 2010
Keywords:
fungal, infection, gene deficient mice, lung, surfactant protein, a fumigatus
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Local EPrints ID: 158123
URI: http://eprints.soton.ac.uk/id/eprint/158123
ISSN: 0161-5890
PURE UUID: 31f27051-b346-4826-8d7a-578aa029ac8e
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Date deposited: 15 Jun 2010 13:19
Last modified: 14 Mar 2024 01:49
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Contributors
Author:
Taruna Madan
Author:
Kenneth B.M. Reid
Author:
Howard Clark
Author:
Mamta Singh
Author:
Annapurna Nayak
Author:
P. Usha Sarma
Author:
Samuel Hawgood
Author:
Uday Kishore
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