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- Title
Type I interferons suppress CD4<sup>+</sup> T-cell-dependent parasite control during blood-stage Plasmodium infection.
- Authors
Haque, Ashraful; Best, Shannon E.; Ammerdorffer, Anne; Desbarrieres, Laure; de Oca, Marcela Montes; Amante, Fiona H.; de Labastida Rivera, Fabian; Hertzog, Paul; Boyle, Glen M.; Hill, Geoffrey R.; Engwerda, Christian R.
- 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.
- Publication
European Journal of Immunology, 2011, Vol 41, Issue 9, p2688
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201141539