title: Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection.
abstract: The combination of the activating killer cell Ig-like receptor 2DS1 (KIR2DS1) expressed by maternal decidual natural killer cells (dNK) and the presence of its ligand, the HLA-C allotype HLA-C2, expressed by fetal trophoblasts, reduces the risk of developing pregnancy complications. However, no molecular or cellular mechanism explains this genetic correlation. Here we demonstrate that KIR2DS1+ dNK acquired higher cytotoxic function than KIR2DS1- dNK when exposed to human cytomegalovirus (HCMV)-infected decidual stromal cells (DSC), particularly when DSCs express HLA-C2. Furthermore, dNK were unable to degranulate or secrete cytokines in response to HCMV-infected primary fetal extravillous trophoblasts. This emphasizes the immunological challenge to clear placental viral infections within the immune-privileged placenta. Activation of dNK through KIR2DS1/HLA-C2 interaction increases their ability to respond to placental HCMV infection and may limit subsequent virus-induced placental pathology. This mechanism is directly related to how KIR2DS1 expressed by dNK reduces development of severe pregnancy complications such as miscarriages and preterm delivery.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.|PhD Program in Experimental Biology and Biomedicine, Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Ângela C
authors.identifier: 0000-0002-6731-8190
authors.initials: ÂC
authors.lastname: Crespo
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138; jlstrom@fas.harvard.edu tilburgs@fas.harvard.edu.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Strominger
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138; jlstrom@fas.harvard.edu tilburgs@fas.harvard.edu.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tilburgs
mesh_terms: D002469:Cell Separation; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003656:Decidua / Q000276:immunology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015236:HLA-C Antigens / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D010920:Placenta / Q000276:immunology* / Q000821:virology; D010929:Placentation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000821:virology; D011256:Pregnancy Outcome; D054340:Receptors, KIR / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000821:virology
chemical_list: D015236:HLA-C Antigens; D007136:Immunoglobulins; C496212:KIR2DS1 protein, human; D054340:Receptors, KIR
keywords: HLA-C; human; immune tolerance; pregnancy; trophoblast