title: Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes.
abstract: Human NK cells are the earliest source of the protective cytokine IFN-gamma when PBMC from nonimmune donors are exposed to Plasmodium falciparum-infected RBC (iRBC) in vitro. In this study, we show that human NK cells form stable conjugates with iRBC but not with uninfected RBC and that induction of IFN-gamma synthesis is dependent on direct contact between the NK cell and the iRBC. NK cells respond to iRBC only in the presence of a source of IL-12/IL-18 and the subset of NK cells that preferentially respond to iRBC express high levels of the lectin-like receptor CD94/NKG2A. There is heterogeneity between donors in their ability to respond to iRBC. DNA analysis has revealed considerable heterogeneity of killer Ig-like receptor (KIR) genotype among the donor population and has identified 21 new KIR allelic variants in the donors of African and Asian descent. Importantly, we find evidence for significant associations between KIR genotype and NK responsiveness to iRBC. This emphasizes the need for large-scale population-based studies to address associations between KIR genotype and susceptibility to malaria.
authors: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Katerina
authors: K
authors: Artavanis-Tsakonas
authors: Konstantina
authors: K
authors: Eleme
authors: Karina L
authors: KL
authors: McQueen
authors: Nathalie W
authors: NW
authors: Cheng
authors: Peter
authors: P
authors: Parham
authors: Daniel M
authors: DM
authors: Davis
authors: Eleanor M
authors: EM
authors: Riley
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002999:Clone Cells; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D020382:Interleukin-18 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D054340:Receptors, KIR
chemical_list: D020382:Interleukin-18; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D018664:Interleukin-12; D007371:Interferon-gamma