title: Brucella abortus induces apoptosis of human T lymphocytes.
abstract: Immune evasion is essential for Brucella abortus to survive in the face of robust adaptive CD4+ T cell response. 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. We report here that B. abortus induces apoptosis of human T lymphocytes, even though invasion 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. We demonstrated that a prototypical B. abortus outer membrane lipoprotein (l-Omp19), but not its unlipidated form, induced T lymphocyte apoptosis. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also induced an increase in T lymphocyte cell death, indicating that the structural component implicated in the phenomenon could be any B. abortus lipoprotein. B. abortus-induced T lymphocyte apoptosis was dependent on the secretion of TNF-α since pre-incubation of T lymphocytes with anti-TNF-α 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.
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral, CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Lis N
authors.initials: LN
authors.lastname: Velásquez
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Delpino
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Ibañez
authors.forename: Lorena M
authors.initials: LM
authors.lastname: Coria
authors.forename: M Cruz
authors.initials: MC
authors.lastname: Miraglia
authors.forename: Romina
authors.initials: R
authors.lastname: Scian
authors.forename: Juliana
authors.initials: J
authors.lastname: Cassataro
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Giambartolomei
authors.forename: Paula
authors.initials: P
authors.lastname: Barrionuevo
mesh_terms: D017209:Apoptosis; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002003:Brucella abortus / Q000472:pathogenicity*; D002006:Brucellosis / Q000382:microbiology; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D008074:Lipoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008074:Lipoproteins; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone