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1 February 2008 Inhibition of Interleukin-12 Production by Trypanosoma brucei in Rat Macrophages
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The immune response of a host infected with Trypanosoma brucei is modulated by trypomastigotes. We examined the changes in cytokine production in T. brucei gambiense (Wellcome strain; WS) infected rats and the influence on production of interleukin (IL)-12 by macrophages. The blood concentration of interferon-γ, tumor necrosis factor–α, and IL-10 increased beginning the second day after infection. However, an increase in IL-12p40 was not observed until 4 days after infection. When spleen macrophages and Kupffer cells harvested from uninfected rats and HS-P cells (a rat macrophagelike cell line) were cocultured with WS, IL-12p40 production did not change. When HS-P cells were cultured with WS, transport of nuclear factor– κB into the nucleus increased. Levels of macrophage colony-stimulating factor (M-CSF) and granulocyte macrophage colony-stimulating factor mRNA in the spleens and livers of WS-infected rats were high in comparison with uninfected rats, suggesting that the WS promotes macrophage proliferation. The level of IL-12p40 mRNA in HS-P cells cocultured with WS increased in response to transfection with a small interfering RNA against M-CSF or addition of anti–M-CSF antibody. These results suggest that the WS inhibits IL-12p40 mRNA production by promoting production of macrophage colony-stimulating factor by macrophages.

Kazuhiko Nishimura, Shinsuke Sakakibara, Kousuke Mitani, Jyoji Yamate, Yoshihiro Ohnishi, and Shinji Yamasaki "Inhibition of Interleukin-12 Production by Trypanosoma brucei in Rat Macrophages," Journal of Parasitology 94(1), 99-106, (1 February 2008).
Received: 14 May 2007; Accepted: 1 July 2007; Published: 1 February 2008

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