title: Role of NKG2D and its ligands in the anti-infectious activity of Vγ9Vδ2 T cells against intracellular bacteria.
abstract: Human Vγ9Vδ2 T cells play a crucial role in early immune response to intracellular pathogens. Their number is drastically increased in the peripheral blood of patients during the acute phase of brucellosis. In vitro, Vγ9Vδ2 T cells exhibit strong cytolytic activity against Brucella-infected cells and impair intracellular growth of Brucella suis in autologous macrophages. Vγ9Vδ2 T cells use cell contact-dependent mechanisms such as the release of lytic granules and Fas-mediated signals to lyse infected macrophages and decrease the development of intracellular Brucella. Although the involvement of the T-cell receptor (TCR) in the triggering of these responses is known, other surface receptors can modulate Vγ9Vδ2 T-cell response. In this study, we have investigated a potential role of NKG2D and its ligands in the anti-infectious activity of human Vγ9Vδ2 T cells against B. suis. We show that the recruitment of NKG2D by its ligands is sufficient to induce cytokine production and the release of lytic granules through PI3K-dependent pathways, but can also increase the TCR-triggered responses of Vγ9Vδ2 T cells. We also demonstrate that the interaction between NKG2D and its main ligand expressed on Brucella-infected macrophages, UL16-binding protein 1 (ULBP1), is involved in the inhibition of bacterium development. Altogether, these results suggest a direct contribution of NKG2D and its ligands to the anti-infectious activity of Vγ9Vδ2 T cells.
authors.affiliation: Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour Santé Montpellier, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bessoles
authors.forename: Ming
authors.initials: M
authors.lastname: Ni
authors.forename: Sara
authors.initials: S
authors.lastname: Garcia-Jimenez
authors.forename: Françoise
authors.initials: F
authors.lastname: Sanchez
authors.forename: Virginie
authors.initials: V
authors.lastname: Lafont
mesh_terms: D002002:Brucella / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002006:Brucellosis / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D020239:Receptor Cross-Talk; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human; C423231:ULBP1 protein, human; D019869:Phosphatidylinositol 3-Kinases