Type I interferons suppress CD4<sup>+</sup> T‐cell‐dependent parasite control during blood‐stage <i>Plasmodium</i> infection
Abstract During blood‐stage Plasmodium infection, large‐scale invasion of RBCs often occurs before the generation of cellular immune responses. In Plasmodium berghei ANKA (PbA)‐infected C57BL/6 mice, CD4 + T cells controlled parasite numbers poorly, instead providing early help to pathogenic CD8 + T...
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| Main Authors: | , , , , , , , , , , |
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| 格式: | Artigo |
| 语言: | 英语 |
| 出版: |
2011
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| 在线阅读: | https://doi.org/10.1002/eji.201141539 https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eji.201141539 |
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| 总结: | Abstract During blood‐stage Plasmodium infection, large‐scale invasion of RBCs often occurs before the generation of cellular immune responses. In Plasmodium berghei ANKA (PbA)‐infected C57BL/6 mice, CD4 + T cells controlled parasite numbers poorly, instead providing early help to pathogenic CD8 + T cells. Expression analysis revealed that the transcriptional signature of CD4 + T cells from PbA‐infected mice was dominated by type I IFN (IFN‐I) and IFN‐γ‐signalling pathway‐related genes. A role for IFN‐I during blood‐stage Plasmodium infection had yet to be established. Here, we observed IFN‐α protein production in the spleen of PbA‐infected C57BL/6 mice over the first 2 days of infection. Mice deficient in IFN‐I signalling had reduced parasite burdens, and displayed none of the fatal neurological symptoms associated with PbA infection. IFN‐I substantially inhibited CD4 + T‐bet + T‐cell‐derived IFN‐γ production, and prevented this emerging Th1 response from controlling parasites. Experiments using BM chimeric mice revealed that IFN‐I signalled predominantly via radio‐sensitive, haematopoietic cells, but did not suppress CD4 + T cells via direct signalling to this cell type. Finally, we found that IFN‐I suppressed IFN‐γ production, and hampered efficient control of parasitaemia in mice infected with non‐lethal Plasmodium chabaudi. Thus, we have elucidated a novel regulatory pathway in primary blood‐stage Plasmodium infection that suppresses CD4 + T‐cell‐mediated parasite control. |
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