Interferon- γ 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 disease during acute Neospora caninum challenge was investigated in BALB/c mice. Groups of female BALB/c mice were infected i.p. with N. caninum tachyzoites concomitant with either: (1) antibody to interferon- γ; (2) recombinant murine interleukin-12; or (3) recombinant murine interleukin-12 plus antibody to interferon- γ. Mice treated with anti-interferon- γ alone had increased morbidity/mortality, decreased body weight, increased foci of liver 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- γ-treated mice was associated with antigen-specific antibody IgG1>IgG2a and a three-fold decreased ratio of antigen-specific interferon- γ : interleukin-4. Mice treated with recombinant murine interleukin-12 had decreased encephalitis and brain parasite load at 3 weeks p.i. compared with control mice treated with PBS. In recombinant murine interleukin-12-treated mice, decreased brain lesions and parasite load were associated with antigen-specific antibody IgG2a>IgG1 and a three-fold increased ratio of antigen-specific interferon- γ : interleukin-4 from splenocytes; the interleukin-12 effect was dependent upon interferon- γ, as indicated by concomitant in vivo interferon- γ neutralisation. By 6 weeks p.i. with N. caninum, there were no differences in brain lesions and parasite load between interleukin-12- and PBS-treated groups, indicating that the effects of interleukin-12 on driving a protective type 1 response were transient. These data indicate a role for interferon- γ, interleukin-12 and type 1 immune responses in control of acute neosporosis in mice.