Brucella abortus induces apoptosis of human T lymphocytes

VELÁSQUEZ, LIS; DELPINO M VICTORIA; IBANEZ ANDRES; CORIA LORENA; MIRAGLIA CRUZ; SCIAN ROMINA; GIAMBARTOLOMEI GUILLERMO; BARRIONUEVO PAULA

MICROBES AND INFECTION

ELSEVIER SCIENCE BV

Año: 2012 p. 639 - 650

1286-4579

Immune evasion is essential for Brucella abortus to survive in the face of robust adaptive CD4þ T cell response. We have previouslydemonstrated that B. abortus can indirectly inhibit CD4þ T cells by down-regulating MHC-II expression and antigen presentation onmacrophages. However, whether B. abortus is able to directly interfere with T lymphocytes is not known. We report here that B. abortus inducesapoptosis of human T lymphocytes, even though invasion of T lymphocytes was low and non-replicative. The ability of heat-killed B. abortus toreproduce the same phenomenon suggested that there was a bacterial structural component involved. We demonstrated that a prototypicalB. abortus outer membrane lipoprotein (L-Omp19), but not its unlipidated form, induced T lymphocyte apoptosis. Moreover, a synthetic lipohexapeptidethat mimics the structure of the protein lipid moiety also induced an increase in T lymphocyte cell death, indicating that thestructural component implicated in the phenomenon could be any B. abortus lipoprotein. B. abortus-induced T lymphocyte apoptosis wasdependent on the secretion of TNF-a since pre-incubation of T lymphocytes with anti-TNF-a 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 immuneresponses.