IL-4 and IL-10 are essential for immunosuppression induced by high molecular weight proteins from Ascaris suum.
The extract from Ascaris suum worms (Asc) impairs Th1 and Th2 responses to a non-related antigen, i.e. ovalbumin (OVA). Its suppressive capacity is due to high molecular weight components present in a gel filtration fraction (PI). This fraction is able to elicit IL-4 and IL-10 secretion. Interestingly enough, it induces anti-PI non-anaphylactic IgG1 synthesis through the action of IL-12/IFN-gamma. Here, we investigated the down-regulation of the immune response to OVA by PI in IL-12, IFN-gamma, IL-4 or IL-10 C57BL/6 knockout mice immunized with OVA+PI in adjuvant. OVA-induced delayed-type hypersensitivity (DTH) reactions, secretion of IL-2 and IFN-gamma, and IgG1, IgG2c and IgE antibody production were suppressed by PI in wild-type mice, as well as in IL-12- or IFN-gamma-deficient mice. In contrast, PI had no effect on anti-OVA IgE production and DTH, and induced only a partial suppression of IgG1 and IFN-gamma in IL-10(-/-) mice. The experiments also showed that IL-4 was involved in the PI-induced suppression of IgG2c antibodies and IL-2 secretion. Finally, down-regulation of IFN-gamma was not seen in mice lacking both IL-4 and IL-10, i.e. IL-4(-/-) mice treated with anti-IL-10 antibodies before immunization. These results exclude the participation of IL-12 and IFN-gamma in PI-induced immunosuppression, and highlight the essential role of IL-10 in the suppression of OVA-specific Th2-related parameters, as well as the cooperation between IL-10 and IL-4 in the suppression of Th1-related parameters.
Souza
Valdênia M O
VM
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1730, 05508-900 São Paulo, SP, Brazil.
Jacysyn
Jacqueline F
JF
Macedo
Mahasti S
MS
D000818:Animals; D017165:Ascaris suum / Q000737:chemistry*; D015801:Helminth Proteins / Q000737:chemistry* / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008970:Molecular Weight; D010047:Ovalbumin / Q000276:immunology
D015801:Helminth Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin