NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium berghei-mediated cerebral malaria.
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-gamma-inducible protein 10, indicating that this chemokine pathway plays an essential role in leukocyte trafficking leading to cerebral disease and fatalities.
Hansen
Diana S
DS
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. hansen@wehi.edu.au
Bernard
Nicholas J
NJ
Nie
Catherine Q
CQ
Schofield
Louis
L
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D054357:Chemokine CXCL10; D020523:Chemokines, CX3C / Q000378:metabolism / Q000494:pharmacology; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D016779:Malaria, Cerebral / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*
D054357:Chemokine CXCL10; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine