Publication Date:
2012-07-07
Description:
It is well established that IFN- is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN- during P. berghei ANKA infection have not been investigated, and it is not known whether IFN- production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN- reporter mice, we show that NK cells dominate the IFN- response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4 + and CD8 + T cells. Importantly, we demonstrate that IFN-–producing CD4 + T cells, but not innate or CD8 + T cells, can promote the development of ECM in normally resistant IFN- –/– mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4 + T cells accumulate within the spleen, lung, and brain of IFN- –/– mice and induce ECM through active IFN- secretion, which increases the accumulation of endogenous IFN- –/– CD8 + T cells within the brain. Depletion of endogenous IFN- –/– CD8 + T cells abrogates the ability of wild-type CD4 + T cells to promote ECM. Finally, we show that IFN- production, specifically by CD4 + T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8 + T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-–producing CD4 + T cells promote the development of ECM during P. berghei ANKA infection.
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
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