title: The human decidual NK-cell response to virus infection: what can we learn from circulating NK lymphocytes?
abstract: NK cells present in the peripheral blood respond rapidly to pathogens or pathogen-infected cells by various means including cytotoxicity and production of cytokines. Whether decidual NK (dNK) cells are able to play a similar role when the pregnant uterus is infected by viruses is still largely unknown. Decidual NK cells are generally considered as poorly cytotoxic when compared to their peripheral blood counterparts. However, we have recently demonstrated that freshly isolated dNK cells from healthy early pregnant uterus do have a cytotoxic potential mediated by the specific engagement of NKp46 activating receptor. We further found that the co-engagement of CD94/NKG2A inhibiting receptor drastically inhibits the cytolytic function of dNK. This latter observation suggests that in situ the CD94/NKG2A receptor interaction with its HLA-E specific ligand is a dominant negative regulatory mechanism that prevents unwanted dNK cell cytotoxicity in non-infected pregnant uterus. How do dNK cells behave when they are activated by virus-infected cells present at the maternal-fetal interface? Largely based on data obtained from circulating NK cells, this review briefly discusses the following questions: Does uterine viral infection promote decidual NK cell proliferative capacity in situ? Are dNK cells able to kill virus-infected autologous decidual target cells and thus limit the virus spreading to the fetus? Which viral-mediated signal(s) and molecular interactions may subvert inhibition of dNK cytotoxic potential? Does uterine viral infection promote decidual NK cell secretion of cytokines and chemokines that boost the anti-viral immune response?
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1043, Toulouse 31300, France. philippe.le-bouteiller@inserm.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Bouteiller
authors.forename: Johan
authors.initials: J
authors.lastname: Siewiera
authors.forename: Ysabel
authors.initials: Y
authors.lastname: Casart
authors.forename: Maryse
authors.initials: M
authors.lastname: Aguerre-Girr
authors.forename: Hicham
authors.initials: H
authors.lastname: El Costa
authors.forename: Alain
authors.initials: A
authors.lastname: Berrebi
authors.forename: Julie
authors.initials: J
authors.lastname: Tabiasco
authors.forename: Nabila
authors.initials: N
authors.lastname: Jabrane-Ferrat
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D001775:Blood Circulation; D003602:Cytotoxicity, Immunologic; D003656:Decidua / Q000276:immunology* / Q000821:virology; D005260:Female; D006801:Humans; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D021041:Placental Circulation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D000956:Antigens, Viral