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 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.
Madan
T
T
Institute of Genomics and Integrative Biology Mall Road, Delhi, India. taruna@igib.res.in
Kaur
S
S
Saxena
S
S
Singh
M
M
Kishore
U
U
Thiel
S
S
Reid
K B M
KB
Sarma
P U
PU
D000818:Animals; D001228:Aspergillosis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D037222:Collectins / Q000378:metabolism*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism
D037222:Collectins; D037601:Mannose-Binding Lectin; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D