Brucella abortus lipoproteins induce apoptosis of human T lymphocytes through TNF-alpha secretion: a potential mechanism for immune subversion.

VELÁSQUEZ, LIS; DELPINO, VICTORIA; IBAÑEZ, ANDRÉS; CORIA, LORENA; MIRAGLIA, CRUZ; SCIAN, ROMINA; CASSATARO, JULIANA; GIAMBARTOLOMEI, GUILLERMO; BARRIONUEVO, PAULA

Lima

Congreso; X Congress of the Latin-American Association of Immunology-ALAI. Inmunoperu 2012.; 2012

Asociación Latinoamericana de Inmunología (ALAI)

In order to survive inside the host, Brucella abortus must trigger different strategies to evade the robust adaptative CD4+ T cell response it elicits. We have previously demonstrated that B. abortus can indirectly inhibit CD4+ T cells by down-regulating MHC-II expression and antigen presentation on macrophages. However, whether B. abortus is able to directly interfere with T lymphocytes is not known. In this study we demonstrated that B. abortus induces apoptosis of human T lymphocytes (P 0.05), even though infection of T lymphocytes was low and non-replicative. The ability of heat-killed B. abortus to reproduce the same phenomenon suggested that there was a bacterial structural component involved. To determine this, we used a prototypical B. abortus outer membrane lipoprotein (L-Omp19) as a model. L-Omp19, but not its unlipidated form (U-Omp19), induced T lymphocyte apoptosis (P 0.05). Moreover, a synthetic lipohexapeptide (Pam3Cys) that mimics the structure of the protein lipid moiety also induced a significant increase in T lymphocyte cell death (P 0.05), indicating that the structural component implicated in the phenomenon could be any B. abortus lipoprotein. Remarkably, T lymphocytes infected with B. abortus were able to secrete significant amounts of PGE2 (P 0.01). However, inhibition of PGE2 synthesis with indomethacin had no effect on the ability of B. abortus to induce T-lymphocyte-apoptosis. On another account, B. abortus and L-Omp19 were also able to induce significant TNF-alpha secretion by T lymphocytes (P 0.01). On this respect, B. abortus-induced apoptosis was dependent on TNF-alpha production since pre-incubation of T lymphocytes with anti-TNF-alpha mAb inhibited the apoptosis of the cells. Overall, these results represent a new mechanism whereby B. abortus by directly inhibiting T cell-mediated responses may evade adaptive immune responses.