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 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-gamma; (2) recombinant murine interleukin-12; or (3) recombinant murine interleukin-12 plus antibody to interferon-gamma. Mice treated with anti-interferon-gamma 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-gamma-treated mice was associated with antigen-specific antibody IgG1 > IgG2a and a three-fold decreased ratio of antigen-specific interferon-gamma: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-gamma:interleukin-4 from splenocytes; the interleukin-12 effect was dependent upon interferon-gamma, as indicated by concomitant in vivo interferon-gamma 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-gamma, interleukin-12 and type 1 immune responses in control of acute neosporosis in mice.
Baszler
T V
TV
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA. baszlert@vetmed.wsu.edu
Long
M T
MT
McElwain
T F
TF
Mathison
B A
BA
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D003048:Coccidiosis / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology*; D015847:Interleukin-4 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D018688:Neospora / Q000276:immunology*; D009500:Neutralization Tests; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma