Vγ9Vδ2 T Cells Impair Intracellular Multiplication of Brucella suis in Autologous Monocytes Through Soluble Factor Release and Contact-Dependent Cytotoxic Effect

Abstract

Human Vγ9Vδ2 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 Vγ9Vδ2 T cells. Using a two-separate-chambers system, we showed that Brucella fraction, as well as isopentenyl pyrophosphate-activated Vγ9Vδ2 T cells, impaired the multiplication of B. suis in differentiated THP-1 cells through TNF-α and IFN-γ release. In the present study, using circulating Vγ9Vδ2 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 Vγ9Vδ2 T cells in part via TNF-α and IFN-γ, this impairment occurring without host cell lysis; 2) unstimulated Vγ9Vδ2 T cells can impair intracellular bacterial multiplication after their activation by soluble factors released by infected monocytes; and 3) activated Vγ9Vδ2 T cells lyse Brucella-infected monocytes in a contact-dependent manner. Taken together, these results provide evidence that Vγ9Vδ2 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 Vγ9Vδ2 T cells could be triggered and respond as antibacterial effector cells in the early stages of Brucella infection.