Interleukin-12 modulates T-cell responses to microfilariae but fails to abrogate interleukin-5-dependent immunity in a mouse model of onchocerciasis.
Infection of mice with microfilariae of Onchocerca lienalis induces high levels of protective immunity to reinfection, which is dependent on interleukin (IL)-5 but not IL-4. Here, we have investigated the effect of exogenous IL-12 administration during either the priming or effector phases of the immune response. When administered during priming, IL-12 induced down-regulation of parasite-specific serum immunoglobulin (Ig)E and up-regulation of IgG2a. Antigen-specific IL-4 responses were strongly suppressed, whilst blood eosinophil levels were partially reduced. When administered during a challenge infection, IL-12 did not significantly influence the balance of antibody isotypes, but partially reduced eosinophil production. Antigen-specific IL-4 responses were again completely ablated. Unusually, interferon-gamma (IFN-gamma) responses were not significantly affected following IL-12 administration, either during priming or after challenge infections. Moreover, despite a fall in antigen-specific IL-5 production, the expression of IL-5-dependent immunity, as determined by reduction in worm recoveries, was fully maintained. These data demonstrate that parasite-induced IL-4 can be abrogated without affecting protective immunity to Onchocerca microfilariae in mice. In view of the established role of IL-4 in pathogenesis, this may have important implications for the development of immunoprophylaxis aimed at microfilariae and the alleviation of pathology in onchocerciasis.
Hogarth
P J
PJ
Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, UK.
Bianco
A E
AE
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009855:Onchocerciasis / Q000276:immunology* / Q000517:prevention & control; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000947:Antigens, Helminth; D007074:Immunoglobulin G; D015848:Interleukin-5; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma