BRUCELLA ABORTUS INDUCES APOPTOSIS OF HUMAN T LYMPHOCYTES THROUGH TNF-α SECRETION: A POTENTIAL MECHANISM FOR IMMUNE SUBVERSION

LIS VELÁSQUEZ; DELPINO M. VICTORIA; ANDRÉS E. IBAÑEZ; CORIA LORENA; MIRAGLIA M CRUZ; SCIAN ROMINA; CASSATARO JULIANA; GIAMBARTOLOMEI GUILLERMO H.; BARRIONUEVO PAULA

Congreso; Inmuno Perú 2012- Asociacion Latinoamericana de Inmunología; 2012

Asociacion Latinoamericana de Inmunología

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 <0.001), 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 (S-Omp19), induced T lymphocyte apoptosis (P <0.001). 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 <0.001), indicating that the structural componentimplicated 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 <0.001). However, inhibition of PGE2 synthesis with indomethacin had no effect on the ability of B. abortus to induce T-lymphocyte-apoptosis. On the other hand, B. abortus and L-Omp19 were also able to induce significant TNF-α secretion by T lymphocytes (P <0.001). On this respect, B. abortus-induced apoptosis was dependent on TNF-production since pre-incubation of T lymphocytes with anti-TNF-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.