Down-regulation of IL-12 p40 gene in Plasmodium berghei-infected mice.

We analyzed the mechanism that causes suppression of IL-12 p40 gene induction during Plasmodium berghei infection. Although IL-12 together with IFN-gamma plays an important role in protection against pathogenic infection, the IL-12 p70 protein production of infected macrophages is lower than that by the uninfected macrophages. We showed in the present study that the induction of IL-12 p40 gene but not IL-12 p35 gene in macrophages of P. berghei-infected mice was profoundly inhibited. The inhibition was induced by interaction with macrophages that had contacted with P. berghei-infected erythrocytes and was mediated by a soluble factor, IL-10. There was comparable activation of NF-kappaB in uninfected and infected cells. The induction of IFN-regulatory factor-1 gene was comparable in transcription level in uninfected and infected cells, while the unidentified complex formation of IFN-regulatory factor-1 was observed in infected cells. Therefore, the inhibition of the IL-12 p40 gene induction appeared to be regulated at transcriptional regulation level of the gene.