PAS-1, a protein affinity purified from Ascaris suum worms, maintains the ability to modulate the immune response to a bystander antigen.
Helminth infections and parasite components have potent immunomodulatory effects on a host's immune system. In the present study, we investigated the effect of PAS-1, a protein component of Ascaris suum adult worms recognized by a monoclonal antibody (MAIP-1), on humoral and cell-mediated responses to a bystander antigen (ovalbumin [OVA]). MAIP-1 recognized only one of the three polypeptide chains of PAS-1, but neutralized the suppressive effect of the whole worm extract on OVA-specific antibody production. PAS-1 inhibited antibody production against a T-cell-dependent, but not a T-cell-independent, antigen in a dose-dependent way. IgM, IgG1, IgG2b, and also IgE and anaphylactic IgG1 levels were downregulated. In addition, PAS-1 inhibited OVA-specific delayed type hypersensitivity reactions in the footpad of mice, showing a potent immunosuppressive activity on both Th1 and Th2 responses that seems to be mediated by the induction of large amounts of IL-10 and IL-4. Indeed, PAS-1-specific spleen cells secreted sevenfold more IL-10 and threefold more IL-4 than OVA-specific cells in response to in vitro restimulation with the respective antigens. In conclusion, we showed that PAS-1, a single protein component from A. suum, maintains all its immunosuppressive properties.
Oshiro
Telma M
TM
Laboratory of Immunopathology, Butantan Institute, São Paulo, Brazil.
Enobe
Cristina S
CS
Araújo
Cláudia A
CA
Macedo
Mahasti S
MS
Macedo-Soares
Maria Fernanda
MF
D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000947:Antigens, Helminth / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D001196:Ascariasis / Q000276:immunology*; D017165:Ascaris suum / Q000737:chemistry / Q000276:immunology*; D024201:Bystander Effect / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D015801:Helminth Proteins; C511899:PAS-1 protein, Ascaris suum; D016753:Interleukin-10; D015847:Interleukin-4