Type I interferons suppress CD4+ T-cell-dependent parasite control during blood-stage Plasmodium infection

Haque, Ashraful, Best, Shannon E., Ammerdorffer, Anne, Desbarrieres, Laure, de Oca, Marcela Montes, Amante, Fiona H., Rivera, Fabian de Labastida, Hertzog, Paul, Boyle, Glen M., Hill, Geoffrey R. and Engwerda, Christian R. (2011) Type I interferons suppress CD4+ T-cell-dependent parasite control during blood-stage Plasmodium infection. European Journal of Immunology, 41 9: 2688-2698. doi:10.1002/eji.201141539


Author Haque, Ashraful
Best, Shannon E.
Ammerdorffer, Anne
Desbarrieres, Laure
de Oca, Marcela Montes
Amante, Fiona H.
Rivera, Fabian de Labastida
Hertzog, Paul
Boyle, Glen M.
Hill, Geoffrey R.
Engwerda, Christian R.
Title Type I interferons suppress CD4+ T-cell-dependent parasite control during blood-stage Plasmodium infection
Formatted title
Type I interferons suppress CD4+ T-cell-dependent parasite control during blood-stage Plasmodium infection
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
1521-4141
Publication date 2011-09
Year available 2011
Sub-type Article (original research)
DOI 10.1002/eji.201141539
Open Access Status Not yet assessed
Volume 41
Issue 9
Start page 2688
End page 2698
Total pages 11
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Language eng
Formatted 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.
Keyword Cytokines
Immune regulation
Interferons
Malaria
T helper cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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