Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex.
NKT cells are specialized cells coexpressing NK and T cell receptors. Upon activation they rapidly produce high levels of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) and are therefore postulated to influence T(H)1/T(H)2 immune responses. The precise role of the CD1/NKT cell pathway in immune response to infection remains unclear. We show here that CD1d-restricted NKT cells from distinct genetic backgrounds differentially influence T(H)1/T(H)2 polarization, proinflammatory cytokine levels, pathogenesis, and fatality in the P. berghei ANKA/rodent model of cerebral malaria. The functional properties of CD1d-restricted NKT cells vary according to expression of loci of the natural killer complex (NKC) located on mouse chromosome 6, which is shown here to be a significant genetic determinant of murine malarial 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
Siomos
Mary-Anne
MA
Buckingham
Lynn
L
Scalzo
Anthony A
AA
Schofield
Louis
L
D000818:Animals; D000941:Antigens / Q000378:metabolism; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism*; D055610:Antigens, CD1d; D000954:Antigens, Surface; D016207:Cytokines / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D016779:Malaria, Cerebral / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010962:Plasmodium berghei; D011506:Proteins / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000954:Antigens, Surface; D016207:Cytokines; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta