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.
Madan
Taruna
T
Institute of Genomics and Integrative Biology, Council for Scientific and Industrial Research, Delhi University Campus, Mall Road, Delhi 110007, India.
Reid
Kenneth B M
KB
Clark
Howard
H
Singh
Mamta
M
Nayak
Annapurna
A
Sarma
P Usha
PU
Hawgood
Samuel
S
Kishore
Uday
U
D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000235:genetics*; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000235:genetics*
D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D