Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice during Plasmodium berghei blood-stage infection.
Mice deficient of functional interferon regulatory factor-1 (IRF-1-/-) by targeted gene disruption infected with a lethal murine malaria strain, Plasmodium berghei ANKA survived longer than its wild-type littermates despite the inability to induce appreciable amounts of interferon-gamma (IFN-gamma) and nitric oxide. In addition, infected IRF-1-/- mice displayed less organ injury with reduced necrosis and inflammation. Both wild-type and IRF-1-/- mice treated with exogenous interleukin-12 (IL-12) suffered extensive organ damage with corresponding up regulation of IFN-gamma, suggesting the pathogenic potential of IL-12 and IFN-gamma. IL-10 is a cytokine produced by CD4+ T lymphocytes belonging to the Th2 subset. Expression of IL-10 in the wild-type mice correlated with the severity of the infection, with higher mRNA expression towards the later stage of infection. In contrast to the wild-type mice, IL-10 levels in the IRF-1-/- mice were induced early in the infection and decreased gradually as the infection progressed. Both untreated and IL-12 treated wild-type mice appeared to follow a Th1-like immune response early in the infection and a Th2-like immune response later in the infection. However, the IRF-1-/- mice were able to launch an altered immune response with a Th2-like immune response early in the infection. These findings suggest that IL-10 expression in the IRF-1-/- mice during the early stage of P. berghei ANKA infection could play an important role in suppressing pathogenic effects of a cell mediated immune response and promoting protective immunity against the parasite.
Tan
R S
RS
Molecular Parasitology Laboratory, Department of Biological Sciences, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.
Kara
A U
AU
Feng
C
C
Asano
Y
Y
Sinniah
R
R
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology*; D018390:Gene Targeting; D050856:Interferon Regulatory Factor-1; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010962:Plasmodium berghei / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide