B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection mediated by the virulence factor IpaD

Abstract

Event Abstract Back to Event B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection mediated by the virulence factor IpaD Katharina Nothelfer1*, Ellen T. Arena1, Laurie Pinaud1, Michel Neunlist2, Ilia Belotserkovsky1, Claude Parsot1, Rubhana Raqib3, Brian Mozeleski1, Philippe J. Sansonetti1 and Armelle Phalipon1* 1 Institut Pasteur, France 2 Centre Hospitalier Universitaire (CHU) Hôtel Dieu, France 3 International Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B), Bangladesh Shigella is a gram-negative enteroinvasive bacterium and the causative agent of bacillary dysentery, an acute recto-colitis. Antibody-mediated natural immunity to Shigella requires several episodes of infection to get primed and is short-lasting, suggesting that the B cell response is functionally impaired. Here we show that upon ex vivo infection of human colonic tissue, invasive S. flexneri interacts with and invades B lymphocytes. We observe the induction of a type three secretion apparatus (T3SA)-dependent B cell death in vitro, both in lamina propria B lymphocytes and the human CL-01 B cell line. This cell death and the parallel reduction of the B cell pool can also be observed in an in vivo mouse infection model. Intriguingly, Shigella-induced B cell death does not require bacterial invasion or injection of virulence effectors via the T3SA in vitro. Instead, the virulence factor IpaD triggers mitochondrial B cell apoptosis in the presence of bacterial co-signals that render B lymphocytes prone to die. We provide evidence that IpaD binds to and induces apoptosis via TLR2, a signaling pathway that has thus far only been considered as a mitogenic stimulus for B lymphocytes. Apoptotic B lymphocytes in close contact with Shigella displaying IpaD are also detected in isolated lymphoid follicles of rectal biopsies of naturally-infected individuals. These findings reveal a novel mechanism of T3SA action to induce B cell death by the binding of a virulence factor and reveal an efficient strategy by which entero-invasive pathogens could impair the priming of a protective immune response. Keywords: Shigella flexneri, B lymphocytes, Apoptosis, TLR2, virulence factor Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Nothelfer K, Arena ET, Pinaud L, Neunlist M, Belotserkovsky I, Parsot C, Raqib R, Mozeleski B, Sansonetti PJ and Phalipon A (2013). B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection mediated by the virulence factor IpaD. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01169 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Katharina Nothelfer, Institut Pasteur, Paris, France, katharina.nothelfer@pasteur.fr Dr. Armelle Phalipon, Institut Pasteur, Paris, France, armelle.phalipon@pasteur.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Katharina Nothelfer Ellen T Arena Laurie Pinaud Michel Neunlist Ilia Belotserkovsky Claude Parsot Rubhana Raqib Brian Mozeleski Philippe J Sansonetti Armelle Phalipon Google Katharina Nothelfer Ellen T Arena Laurie Pinaud Michel Neunlist Ilia Belotserkovsky Claude Parsot Rubhana Raqib Brian Mozeleski Philippe J Sansonetti Armelle Phalipon Google Scholar Katharina Nothelfer Ellen T Arena Laurie Pinaud Michel Neunlist Ilia Belotserkovsky Claude Parsot Rubhana Raqib Brian Mozeleski Philippe J Sansonetti Armelle Phalipon PubMed Katharina Nothelfer Ellen T Arena Laurie Pinaud Michel Neunlist Ilia Belotserkovsky Claude Parsot Rubhana Raqib Brian Mozeleski Philippe J Sansonetti Armelle Phalipon Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.