PAS-1, a protein from Ascaris suum, modulates allergic inflammationvia IL-10 and IFN-c, but not IL-12

Helminths and their products have a profound immunomodulatory effect upon the inductive and effectorphases of inflammatory responses, including allergy. We have demonstrated that PAS-1, a protein isolatedfrom Ascaris suum worms, has an inhibitory effect on lung allergic inflammation due to its abilityto down-regulate eosinophilic inflammation, Th2 cytokine release and IgE antibody production. Here,we investigated the role of IL-12, IFN-c and IL-10 in the PAS-1-induced inhibitory mechanism using amurine model of asthma. Wild type C57BL/6, IL-12 / , IFN-c / and IL-10 / mice were immunized withPAS-1 and/or OVA and challenged with the same antigens intranasally. The suppressive effect of PAS-1was demonstrated on the cellular influx into airways, with reduction of eosinophil number and eosinophilperoxidase activity in OVA + PAS-1-immunized wild type mice. This effect well correlated with a significantreduction in the levels of IL-4, IL-5, IL-13 and eotaxin in BAL fluid. Levels of IgE and IgG1antibodies were also impaired in serum from these mice. The inhibitory activity of PAS-1 was alsoobserved in IL-12 / mice, but not in IFN-c / and IL-10 / animals. These data show that IFN-c andIL-10, but not IL-12, play an important role in the PAS-1 modulatory effect.

Early stages ofAscaris suuminduce airway inflammation andhyperreactivity in a mouse model

The inflammatory and functional changes that occur in murinelung after infection with 2500 infectiveAscaris suumeggswere studied in this work. A sequential influx of neutrophils,mononuclear cells and eosinophils occurred into airwaysconcomitantly with migration of larvae from liver to thelungs. Histological analysis of the lung showed a severe intraalveolarhaemorrhage at the peak of larval migration (day 8)and the most intense inflammatory cell infiltrate on day 14.AscarisL3 were found in alveolar spaces and inside bronchioleson day 8. The number of eosinophils was elevated inthe blood on days 8 and 14. The peak of eosinophil influx intothe lung was at day 14, as indicated by the high levels of eosinophilperoxidase activity, followed by their migration into theairways. The antibody response against egg and larval antigensconsisted mainly of IgG1 and IgM, and also of IgE andanaphylactic IgG1, that cross-reacted with adult worm antigens.Total IgE levels were substantially elevated during theinfection. Measurement of lung mechanical parametersshowed airway hyperreactivity in infected mice. In conclusion,the murine model ofA. suuminfection mimics the Th2-induced parameters observed in pigs and humans and can beused to analyse the immunoregulatory properties of thishelminth.