GIAMBARTOLOMEI Guillermo Hernan
congresos y reuniones científicas
Brucella abortus induces apoptosis of human T lymphocytes: a potential mechanism for chronic infection.
VELÁSQUEZ L DELPINO MV GARCÍA SAMARTINO C. IBAÑEZ A CORIA L CASSATARO J GIAMBARTOLOMEI G H BARRIONUEVO P
Congreso; 1er Congreso Franco-Argentino de Inmunología; 2010
Despite its ability to generate a vigorous Th1 response, Brucella abortus can persist inside macrophages and establish a chronic infection. We have recently demonstrated that B. abortus inhibits the IFN-ã-induced expression of MHC-II and antigen presentation on human monocytes. In this study, we evaluated whether this microorganism can directly affect the response/activation of T lymphocytes (TL). We first investigated if TL could be infected with B. abortus. In order to evaluate this, purified human TL were incubated with B. abortus at different ratios of B. abortus to TL. B. abortus was unable to infect TL, even at the highest ratio used. Next, we evaluated if B. abortus could affect the activation of TL. In this respect, purified TL were stimulated with plate-bound anti-CD3 for 48 h in the presence of B. abortus. IFN-ã and IL-2 production and T-cell proliferation were then measured. B. abortus inhibited significantly (p<0.05) the proliferation and the secretion of IFN-ã and IL-2 in a dose-dependent manner. Since a defect on T-cell proliferation after the infection with other pathogens has been reported to be related to T-cell apoptosis, we next investigated whether B. abortus could also induce this phenomenon. Purified TL were incubated with B. abortus for 24 h, 48 h and 5 days. After this, cells were stained with Annexin V/PI and apoptosis was determined by flow cytometry. B. abortus induced increased apoptosis of TL at 48 h and 5 days, in a dose-dependent manner (% Annexin V+ cells at 5-day. Medium 29%; 50:1 52%; 100:1 64%; 1000:1 77%). Furthermore, heat-killed B. abortus (HKBA) also induced elevated T-cell apoptosis indicating that a structural component of the bacterium is implicated in this effect. Together, these results suggest that the diminished activation of T lymphocytes could be related to an increased susceptibility to apoptosis and, that this could be considered as another possible mechanism by which B. abortus evades the immune system.