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

• Published in: Molecular immunology 2010-06, Vol.47 (10), p.1923-1930
• Main Authors: Madan, Taruna, Reid, Kenneth B.M., Clark, Howard, Singh, Mamta, Nayak, Annapurna, Sarma, P. Usha, Hawgood, Samuel, Kishore, Uday
• Format: Article
• Language: English
• Subjects: A. fumigatus; Animals; Aspergillus fumigatus; Fungal; Gene deficient mice; Genetic Predisposition to Disease; Humans; Infection; Invasive Pulmonary Aspergillosis - genetics; Lung; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Surfactant-Associated Protein A - deficiency; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein D - deficiency; Pulmonary Surfactant-Associated Protein D - genetics; Surfactant protein
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2010.02.027

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-α and IFN-γ 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-γ 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.