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The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
NK cells are cytotoxic lymphocytes that also secrete regulatory cytokines and can therefore influence adaptive immune responses. NK cell function is largely controlled by genes present in a genomic region named the NK complex. It has been shown that the NK complex is a genetic determinant of murine cerebral malaria pathogenesis mediated by Plasmodium berghei ANKA. In this study, we show that NK cells are required for cerebral malaria disease induction and the control of parasitemia. NK cells were found infiltrating brains of cerebral malaria-affected mice. NK cell depletion resulted in inhibition of T cell recruitment to the brain of P. berghei-infected animals. NK cell-depleted mice displayed down-regulation of CXCR3 expression and a significant reduction of T cells migrating in response to IFN-
-inducible protein 10, indicating that this chemokine pathway plays an essential role in leukocyte trafficking leading to cerebral disease and fatalities.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Health and Medical Research Council (Australia) Project Grant 356239 and Program Grant 215201. L.S. is an International Research Scholar of the Howard Hughes Medical Institute.
2 Address correspondence and reprint requests to Dr. Diana S. Hansen, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. E-mail address: hansen{at}wehi.edu.au
3 Abbreviations used in this paper: DC, dendritic cell; NKC, NK complex; MHC I, MHC class I; LT-
, lymphotoxin-; p.i., postinfection; IP-10, IFN--inducible protein 10; MIG, monokine induced by IFN-; I-TAC, IFN-inducible -chemoattractant; BSL, brain-sequestered leukocyte.
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