Interferon-gamma and interleukin-12 mediate protection to acute Neospora caninum infection in BALB/c mice

The type of immune response required to protect mice against clinical disea se during acute Neospora caninum challenge was investigated in BALB/c mice. Groups of female BALB/c mice were infected i.p. with N. caninum tachyzoite s concomitant with either: (I) antibody to interferon-gamma; (2) recombinan t murine interleukin-12; or (3) recombinant murine interleukin-12 plus anti body to interferon-gamma. Mice treated with anti-interferon-gamma alone had increased morbidity/mortality, decreased body weight, increased foci of li ver necrosis and increased numbers of N. caninum tachyzoites in the lung by 7 days p.i. compared with controls. Increased disease and parasite load in the anti-interferon-gamma-treated mice was associated with antigen-specifi c antibody IgG1 > IgG2a and a three-fold decreased ratio of antigen-specifi c interferon-gamma :interleukin-4. Mice treated with recombinant murine int erleukin-12 had decreased encephalitis and brain parasite load at 3 weeks p .i. compared with control mice treated with PBS. In recombinant murine inte rleukin-12-treated mice, decreased brain lesions and parasite load were ass ociated with antigen-specific antibody IgG2a > IgG1 and a three-fold increa sed ratio of antigen-specific interferon-gamma : interleukin-4 from splenoc ytes; the interleukin-12 effect was dependent upon interferon-gamma, as ind icated by concomitant in vivo interferon-gamma neutralisation. By 6 weeks p .i. with N. caninum, there were no differences in brain lesions and parasit e load between interleukin-IZ and PBS-treated groups, indicating that the e ffects of interleukin-12 on driving a protective type 1 response were trans ient. These data indicate a role for interferon-gamma, interleukin-12 and t ype 1 immune responses in control of acute neosporosis in mice. (C) 1999 Au stralian Society for Parasitology Inc. Published by Elsevier Science Ltd. A ll rights reserved.