Transforming growth factor beta-induced failure of resistance to infection with blood-stage Plasmodium chabaudi in mice.
The role of transforming growth factor beta (TGF-beta) in infection with Plasmodium chabaudi was investigated with resistant and susceptible mouse models. C57BL/10 mice produced gamma interferon (IFN-gamma) and nitric oxide (NO) shortly after infection and cleared the parasite spontaneously. In contrast, BALB/c mice showed a transient enhancement of TGF-beta production, followed by a relative lack of IFN-gamma and NO production, and succumbed to the infection. However, there was no correlation between levels of serum TGF-beta and splenic TGF-beta mRNA in both mouse strains before and after infection. Administration of recombinant TGF-beta (rTGF-beta) rendered resistant mice susceptible because of suppression of subsequent production of IFN-gamma and NO. Administration of anti-TGF-beta antibody to the infected BALB/c mice resulted in remarkable increases in serum IFN-gamma and NO, and the mice resisted the infection. Splenic CD4(+) T and CD11b+ cells of C57BL/10 mice were significantly activated after infection, but this was completely abrogated by administration of rTGF-beta. These results suggested that, in the P. chabaudi-susceptible but not resistant mice, production of TGF-beta was promoted, and subsequent failure of IFN-gamma- and NO-dependent resistance to the parasite was induced. This study is the first to indicate that TGF-beta production was the key event in failure of resistance to mouse malaria.
Tsutsui
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Department of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
Kamiyama
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T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D016788:Plasmodium chabaudi / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse