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‐γ) and...

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Bibliographic Details
Published in:Parasite immunology 2000-09, Vol.22 (9), p.425-435
Main Authors: Tan, Rosemary S.‐P., Kara, Anna U., Feng, Chiguang, Asano, Yoshihiro, Sinniah, Raja
Format: Article
Language:English
Subjects:
Animals
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Erythrocytes - parasitology
g-Interferon
Gene Targeting
Interferon Regulatory Factor-1
Interleukin-10 - genetics
Interleukin-10 - metabolism
Interleukin-12 - administration & dosage
Interleukin-12 - genetics
Interleukin-12 - metabolism
interleukin‐10
interleukin‐12
Kidney - immunology
Kidney - pathology
Liver - immunology
Liver - pathology
Malaria - immunology
Malaria - parasitology
Malaria - pathology
Malaria - physiopathology
Mice
Mice, Inbred C57BL
nitric oxide
Nitric Oxide - metabolism
Phosphoproteins - deficiency
Phosphoproteins - genetics
Phosphoproteins - metabolism
Plasmodium berghei
Plasmodium berghei - immunology
Recombinant Proteins - administration & dosage
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Spleen - immunology
Spleen - pathology
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
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Summary: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‐γ) 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‐γ, suggesting the pathogenic potential of IL‐12 and IFN‐γ. 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.
ISSN:0141-9838
1365-3024
DOI:10.1046/j.1365-3024.2000.00312.x