Related Experiment Video
Updated: Jul 28, 2026
Isolation and Analysis of Brain-sequestered Leukocytes from Plasmodium berghei ANKA-infected Mice
Published on: January 2, 2013
Down-regulation of IL-12 p40 gene in Plasmodium berghei-infected mice
1Department of Immunology and Host Defenses, Ehime University School of Medicine, Ehime, Japan.
Abstract:
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.
Insights
Plasmodium berghei infection suppresses interleukin-12 (IL-12) p40 gene induction in macrophages. This suppression is mediated by interleukin-10 (IL-10), impacting anti-parasitic immune responses.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Interleukin-12 (IL-12) and Interferon-gamma (IFN-gamma) are crucial for controlling parasitic infections.
- Macrophages infected with Plasmodium berghei exhibit reduced IL-12 p70 protein production compared to uninfected cells.
Purpose of the Study:
- To elucidate the mechanism behind the suppressed IL-12 p40 gene induction during Plasmodium berghei infection.
- To identify the factors and regulatory pathways involved in this immune suppression.
Main Methods:
- Analysis of IL-12 p40 and p35 gene induction in macrophages from P. berghei-infected mice.
- Investigation of the role of macrophage interaction with infected erythrocytes.
- Assessment of soluble factors, including IL-10, mediating the suppression.
- Evaluation of NF-kappaB activation and IFN-regulatory factor-1 (IRF-1) gene expression and complex formation.
Main Results:
- Profound inhibition of IL-12 p40 gene induction, but not IL-12 p35, in P. berghei-infected macrophages.
- Suppression mediated by a soluble factor, identified as IL-10, triggered by macrophage contact with infected erythrocytes.
- Comparable NF-kappaB activation in both infected and uninfected cells.
- Similar transcriptional levels of IRF-1, but altered complex formation in infected cells, suggesting transcriptional regulation.
Conclusions:
- The suppression of IL-12 p40 gene induction during P. berghei infection is primarily regulated at the transcriptional level.
- IL-10 plays a key role in mediating this suppression, contributing to impaired anti-parasitic immunity.
- Altered IRF-1 complex formation may contribute to the dysregulated immune response observed in malaria infection.
