Premium
Resistant mice lacking interleukin‐12 become susceptible to Trypanosoma cruzi infection but fail to mount a T helper type 2 response
Author(s) -
Galvão Da Silva Ana Paula,
Jacysyn Jacqueline F.,
Abrahamsohn Ises De Almeida
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01571.x
Subject(s) - trypanosoma cruzi , biology , cytokine , knockout mouse , immunology , interferon gamma , interleukin 4 , nitric oxide , interleukin 12 , immune system , microbiology and biotechnology , cytotoxic t cell , in vitro , parasite hosting , endocrinology , receptor , biochemistry , world wide web , computer science
Summary Interleukin‐12 (IL‐12) is essential to resistance to Trypanosoma cruzi infection because it stimulates the synthesis of interferon‐γ (IFN‐γ) that activates macrophages to a parasiticidal effect. Investigation of mice deprived of IL‐12 genes (IL‐12 knockout mice) has confirmed the important role of IL‐12 and IFN‐γ in controlling parasitism in T. cruzi infection. However, it has not yet been addressed whether a shift towards a T helper type 2 (Th2) pattern of cytokine response occurred in these mice that might have contributed to the aggravation of the infection caused by IL‐12 deprivation. We examined the course of T. cruzi (Y strain) infection and the regulation of cytokine responses and nitric oxide production in C57BL/6 IL‐12 p40‐knockout mice. The mutant mice were extremely susceptible to the infection as evidenced by increased parasitaemia, tissue parasitism and mortality in comparison with the control C57BL/6 mouse strain (wild‐type) that is resistant to T. cruzi . A severe depletion of parasite‐antigen‐specific IFN‐γ response, without an increase in IL‐4 or IL‐10 production, accompanied by reduced levels of nitric oxide production was observed in IL‐12 knockout mice. We found no evidence of a shift towards a Th2‐type cytokine response. In IL‐12 knockout mice, the residual IFN‐γ production is down‐regulated by IL‐10 but not by IL‐4 and nitric oxide production is stimulated by tumour necrosis factor‐α. Parasite‐specific immunoglobulin G1 antibody levels were similar in IL‐12 knockout and wild‐type mice, whereas IL‐12 knockout mice had much higher levels of immunoglobulin G2b.