B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection. Nothelfer, K., Arena, E. T., Pinaud, L., Neunlist, M., Mozeleski, B., Belotserkovsky, I., Parsot, C., Dinadayala, P., Burger-Kentischer, A., Raqib, R., Sansonetti, P. J., & Phalipon, A. The Journal of Experimental Medicine, 211(6):1215--1229, June, 2014.
doi  abstract   bibtex   
Antibody-mediated immunity to Shigella, the causative agent of bacillary dysentery, requires several episodes of infection to get primed and is short-lasting, suggesting that the B cell response is functionally impaired. We show that upon ex vivo infection of human colonic tissue, invasive S. flexneri interacts with and occasionally invades B lymphocytes. The induction of a type three secretion apparatus (T3SA)-dependent B cell death is observed in the human CL-01 B cell line in vitro, as well as in mouse B lymphocytes in vivo. In addition to cell death occurring in Shigella-invaded CL-01 B lymphocytes, we provide evidence that the T3SA needle tip protein IpaD can induce cell death in noninvaded cells. IpaD binds to and induces B cell apoptosis via TLR2, a signaling receptor thus far considered to result in activation of B lymphocytes. The presence of bacterial co-signals is required to sensitize B cells to apoptosis and to up-regulate tlr2, thus enhancing IpaD binding. Apoptotic B lymphocytes in contact with Shigella-IpaD are detected in rectal biopsies of infected individuals. This study therefore adds direct B lymphocyte targeting to the diversity of mechanisms used by Shigella to dampen the host immune response.
@article{ nothelfer_b_2014,
  title = {B lymphocytes undergo {TLR}2-dependent apoptosis upon {Shigella} infection},
  volume = {211},
  doi = {10.1084/jem.20130914},
  abstract = {Antibody-mediated immunity to Shigella, the causative agent of bacillary dysentery, requires several episodes of infection to get primed and is short-lasting, suggesting that the B cell response is functionally impaired. We show that upon ex vivo infection of human colonic tissue, invasive S. flexneri interacts with and occasionally invades B lymphocytes. The induction of a type three secretion apparatus (T3SA)-dependent B cell death is observed in the human CL-01 B cell line in vitro, as well as in mouse B lymphocytes in vivo. In addition to cell death occurring in Shigella-invaded CL-01 B lymphocytes, we provide evidence that the T3SA needle tip protein IpaD can induce cell death in noninvaded cells. IpaD binds to and induces B cell apoptosis via TLR2, a signaling receptor thus far considered to result in activation of B lymphocytes. The presence of bacterial co-signals is required to sensitize B cells to apoptosis and to up-regulate tlr2, thus enhancing IpaD binding. Apoptotic B lymphocytes in contact with Shigella-IpaD are detected in rectal biopsies of infected individuals. This study therefore adds direct B lymphocyte targeting to the diversity of mechanisms used by Shigella to dampen the host immune response.},
  language = {en},
  number = {6},
  journal = {The Journal of Experimental Medicine},
  author = {Nothelfer, Katharina and Arena, Ellen T. and Pinaud, Laurie and Neunlist, Michel and Mozeleski, Brian and Belotserkovsky, Ilia and Parsot, Claude and Dinadayala, Premkumar and Burger-Kentischer, Anke and Raqib, Rubhana and Sansonetti, Philippe J. and Phalipon, Armelle},
  month = {June},
  year = {2014},
  pages = {1215--1229}
}

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