GIAMBARTOLOMEI Guillermo Hernan
congresos y reuniones científicas
Brucella abortus Lipoproteins induce apoptosis of human T lymphocytes through TNF-α secretion: a potential mechanism for immune subversion.
VEL&AACUTE;SQUEZ L. N.; DELPINO M. V., IB&AACUTE;&NTILDE;EZ A., CORIA L., MIRAGLIA M. C., SCIAN R., CASSATARO J., GIAMBARTOLOMEI G. H., BARRIONUEVO P
Congreso; 10th Latin American Congress of Immunology.; 2012
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-£ secretion by T lymphocytes (P <0.001). On this respect, B. abortus-induced apoptosis was dependent on TNF-?Ñ?nproduction since pre-incubation of T lymphocytes with anti-TNF-?Ñ?nmAb 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.