PAS-1, a protein from Ascaris suum, modulates allergic inflammation via IL-10 and IFN-gamma, but not IL-12.
Helminths and their products have a profound immunomodulatory effect upon the inductive and effector phases of inflammatory responses, including allergy. We have demonstrated that PAS-1, a protein isolated from Ascaris suum worms, has an inhibitory effect on lung allergic inflammation due to its ability to down-regulate eosinophilic inflammation, Th2 cytokine release and IgE antibody production. Here, we investigated the role of IL-12, IFN-gamma and IL-10 in the PAS-1-induced inhibitory mechanism using a murine model of asthma. Wild type C57BL/6, IL-12(-/-), IFN-gamma(-/-) and IL-10(-/-) mice were immunized with PAS-1 and/or OVA and challenged with the same antigens intranasally. The suppressive effect of PAS-1 was demonstrated on the cellular influx into airways, with reduction of eosinophil number and eosinophil peroxidase activity in OVA+PAS-1-immunized wild type mice. This effect well correlated with a significant reduction in the levels of IL-4, IL-5, IL-13 and eotaxin in BAL fluid. Levels of IgE and IgG1 antibodies were also impaired in serum from these mice. The inhibitory activity of PAS-1 was also observed in IL-12(-/-) mice, but not in IFN-gamma(-/-) and IL-10(-/-) animals. These data show that IFN-gamma and IL-10, but not IL-12, play an important role in the PAS-1 modulatory effect.
Araújo
C A
CA
Laboratory of Immunopathology, Butantan Institute, Av Vital Brasil 1500, 05503-900 São Paulo SP, Brazil.
Perini
A
A
Martins
M A
MA
Macedo
M S
MS
Macedo-Soares
M F
MF
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D015801:Helminth Proteins / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D015801:Helminth Proteins; D007074:Immunoglobulin G; C511899:PAS-1 protein, Ascaris suum; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma