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

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02874954
Contributor : Armelle Phalipon <>
Submitted on : Friday, June 19, 2020 - 12:18:11 PM
Last modification on : Wednesday, October 14, 2020 - 4:01:01 AM

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Katharina Nothelfer, Ellen Arena, Laurie Pinaud, Michel Neunlist, Ilia Belotserkovsky, et al.. B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection mediated by the virulence factor IpaD. 15th International Congress of Immunology (ICI), Aug 2013, Milan, Italy. pp.1-36, ⟨10.3389/conf.fimmu.2013.02.01169⟩. ⟨pasteur-02874954⟩

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