Inhibition of interleukin-12 production by Trypanosoma brucei in rat macrophages.
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-gamma, tumor necrosis factor-alpha, 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-kappaB 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.
Nishimura
Kazuhiko
K
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan. nisimura@vet.osakafu-u.ac.jp
Sakakibara
Shinsuke
S
Mitani
Kousuke
K
Yamate
Jyoji
J
Ohnishi
Yoshihiro
Y
Yamasaki
Shinji
S
D000818:Animals; D018920:Coculture Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D007728:Kupffer Cells / Q000166:cytology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014347:Trypanosoma brucei gambiense / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor