Interleukin-12-mediated resistance to Trypanosoma cruzi is dependent on tumor necrosis factor alpha and gamma interferon.
The aim of this study was to determine if interleukin-12 (IL-12) has a role in the immune response to Trypanosoma cruzi. Infection of BALB/c mice with the virulent Tulahuen strain of T. cruzi is characterized by a high-level parasitemia, pathology in the heart associated with the presence of amastigotes, and death during the acute phase of the disease. Administration of IL-12 to BALB/c mice infected with T. cruzi resulted in a reduced parasitemia and a significant delay in the time to death compared with those for infected controls. This protective effect was correlated with increased levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in serum. To determine if these cytokines were involved in the protective effects of IL-12, we treated infected mice with IL-12 alone or in combination with monoclonal antibodies specific for IFN-gamma or TNF-alpha. These antibodies antagonized the protective effect of exogenous IL-12. Treatment of infected mice with a polygonal antibody specific for IL-12 resulted in a significant increase in parasitemia but did not affect the time to death. These latter studies demonstrate a role for endogenous IL-12 in resistance to T. cruzi. Together, our data identify an IL-12-mediated mechanism of resistance to T. cruzi, which is dependent on IFN-gamma and TNF-alpha.
Hunter
C A
CA
Department of Immunology and Infectious Disease, Research Institute, Palo Alto Medical Foundation, California 94301, USA.
Slifer
T
T
Araujo
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D014355:Chagas Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D018664:Interleukin-12 / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000276:immunology / Q000628:therapy; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma