Role of collectins in innate immunity against aspergillosis

The protective role of lung surfactant proteins SP-A, SP-D and MBL in the host defense against both allergic and invasive aspergillosis was identified and established by a series of in vitro and in vivo studies. Therapeutic administration of SP-D and MBL proteins in a murine model of pulmonary invas...

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Published in:Medical mycology (Oxford) 2005, Vol.43 (S1), p.155-163
Main Authors: Madan, T., Kaur, S., Saxena, S., Singh, M., Kishore, U., Thiel, S., Reid, K.B.M., Sarma, P.U.
Format: Article
Language:English
Subjects:
Animals
Aspergillosis - genetics
Aspergillosis - immunology
Aspergillosis - mortality
Aspergillosis, Allergic Bronchopulmonary - genetics
Aspergillosis, Allergic Bronchopulmonary - immunology
Aspergillosis, Allergic Bronchopulmonary - mortality
Aspergillus
Aspergillus fumigatus - pathogenicity
Collectins - metabolism
Disease Models, Animal
Genetic Predisposition to Disease
Humans
Immunity, Innate
Mannose-Binding Lectin - genetics
Mannose-Binding Lectin - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Polymorphism, Single Nucleotide
Pulmonary Surfactant-Associated Protein A - genetics
Pulmonary Surfactant-Associated Protein A - metabolism
Pulmonary Surfactant-Associated Protein D - genetics
Pulmonary Surfactant-Associated Protein D - metabolism
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Summary:The protective role of lung surfactant proteins SP-A, SP-D and MBL in the host defense against both allergic and invasive aspergillosis was identified and established by a series of in vitro and in vivo studies. Therapeutic administration of SP-D and MBL proteins in a murine model of pulmonary invasive aspergillosis rescued mice from death. In mice mimicking human allergic bronchopulmonary aspergillosis, SP-A and SP-D suppressed IgE levels, eosinophilia, pulmonary cellular infiltration and cause a marked shift from a pathogenic Th2 to a protective Th1 cytokine profile. SP-A and SP-D knock-out mice studies made significant contributions in understanding the mechanisms by which SP-A and SP-D modulate the host defense response in patients suffering from pulmonary allergies and infections. The results suggested that individuals with any structural or functional defects in these innate immune molecules due to genetic variations might be susceptible to aspergillosis. SNPs in SP-A2 and MBL genes showed significant associations with patients of allergic bronchopulmonary aspergillosis in an Indian population. The patients carrying either one or both of GCT and AGG alleles of SP-A2 and patients with A allele at position 1011 of MBL had markedly higher eosinophilia, total IgE antibodies and lower FEV1 (the clinical markers of ABPA). Our results show that collectins play an important role in Aspergillus mediated allergies and infections.
ISSN:1369-3786
1460-2709
DOI:10.1080/13693780500088408