title: Plasmodium falciparum-infected erythrocytes and IL-12/IL-18 induce diverse transcriptomes in human NK cells: IFN-α/β pathway versus TREM signaling.
abstract: The protective immunity of natural killer (NK) cells against malarial infections is thought to be due to early production of type II interferon (IFN) and possibly direct NK cell cytotoxicity. To better understand this mechanism, a microarray analysis was conducted on NK cells from healthy donors PBMCs that were co-cultured with P. falciparum 3D7-infected erythrocytes. A very similar pattern of gene expression was observed among all donors for each treatment in three replicas. Parasites particularly modulated genes involved in IFN-α/β signaling as well as molecules involved in the activation of interferon regulatory factors, pathways known to play a role in the antimicrobial immune response. This pattern of transcription was entirely different from that shown by NK cells treated with IL-12 and IL-18, in which IFN-γ- and TREM-1-related genes were over-expressed. These results suggest that P. falciparum parasites and the cytokines IL-12 and IL-18 have diverse imprints on the transcriptome of human primary NK cells. IFN-α-related genes are the prominent molecules induced by parasites on NK cells and arise as candidate biomarkers that merit to be further investigated as potential new tools in malaria control.
authors.affiliation: Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany. elisandragc@gmail.com
authors.forename: Elisandra
authors.initials: E
authors.lastname: Grangeiro de Carvalho
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D019295:Computational Biology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016898:Interferon-alpha; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D018664:Interleukin-12; D007371:Interferon-gamma