V gamma 9V delta 2 T cells impair intracellular multiplication of Brucella suis in autologous monocytes through soluble factor release and contact-dependent cytotoxic effect.
Human Vgamma9Vdelta2 T cells are considered to play an important role in brucellosis, as this population is dramatically increased in peripheral blood of patients during the acute phase of the infection. This T lymphocyte population has been largely demonstrated to be activated by small m.w. nonpeptidic molecules from natural or synthetic origin. We recently identified a nonpeptidic fraction of Brucella suis that specifically activates human Vgamma9Vdelta2 T cells. Using a two-separate-chambers system, we showed that Brucella fraction, as well as isopentenyl pyrophosphate-activated Vgamma9Vdelta2 T cells, impaired the multiplication of B. suis in differentiated THP-1 cells through TNF-alpha and IFN-gamma release. In the present study, using circulating Vgamma9Vdelta2 T cells and autologous monocytes infected with B. suis, we provide evidence that 1) intramonocytic multiplication of B. suis is impaired by supernatants of activated Vgamma9Vdelta2 T cells in part via TNF-alpha and IFN-gamma, this impairment occurring without host cell lysis; 2) unstimulated Vgamma9Vdelta2 T cells can impair intracellular bacterial multiplication after their activation by soluble factors released by infected monocytes; and 3) activated Vgamma9Vdelta2 T cells lyse Brucella-infected monocytes in a contact-dependent manner. Taken together, these results provide evidence that Vgamma9Vdelta2 T cells, in addition to being directly activated by soluble nonpeptidic molecules, can be stimulated to become highly cytotoxic in the specific presence of infected monocytes; moreover, they suggest how Vgamma9Vdelta2 T cells could be triggered and respond as antibacterial effector cells in the early stages of Brucella infection.
Ottones
F
F
Institut National de la Santé et de la Recherche Médicale Unité 431, Microbiologie et Pathologie Cellulaire Infectieuse, Université de Montpellier II, Montpellier, France.
Dornand
J
J
Naroeni
A
A
Liautard
J P
JP
Favero
J
J
D001770:Blood Bactericidal Activity / Q000276:immunology*; D002002:Brucella / Q000254:growth & development* / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002474:Cell-Free System / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma