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Project #14510
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#14510 : Shigella targeting of human colonic Lamina Propria Mononuclear Cells
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Name of Applicant : Katja Brunner
Date of application : 12-11-2019
Unit : Molecular Microbial Pathogenesis
Location : Dulaux, Bertrand wing, 1ere etage, Room 06A
Phone : 0140613771
@ Mail : katja.brunner@pasteur.fr
@ PI-Mail : armelle.phalipon@pasteur.fr

Project context and summary :

The enteropathogen, Shigella, is highly virulent and remarkably adjusted to the intestinal environment of its almost exclusive human host. Key for Shigella pathogenicity is the injection of virulence effectors into the host cell, via its type three secretion system (T3SS), initiating disease onset and progression. T3SS-mediated host cell targeting is associated with Shigella invasion and dissemination in epithelial cells. Yet, our group reported the direct targeting of human lymphocytes by an injection-only mechanisms, i.e. the injection of Shigella T3SS effectors without subsequent cell invasion. To further investigate the scope and selectivity of this targeting mechanism, we utilised human lamina propria mononuclear cells (LPMCs) isolated from colonic explants and peripheral blood mononuclear cells (PBMCs) and assessed the mode of Shigella targeting by the use of a T3SS reporter stain and multiparametric CyTOF technology. In human LPMCs, a population of CD38hi plasma cells/ plasmablasts was identified as primarily targeted and presented up to 80% of all targeted LPMCs. Interestingly, plasma cells constitute the primary IgA-producing cell type and IgA has been previously identified as important mediator of Shigella pathogenicity. The functional implications on plasma cell targeting by Shigella is subject of current investigations.


Related team publications :
Pinaud et al. (2017), PNAS, 114 (37): 9954-9959
Brunner et al. (2019), Hum Vaccin Immunother., 15(6): 1317–1325.
Bossel Ben-Moshe (2019), Nat Commun., 10(1):3266.
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