Shigella impairs human T lymphocyte responsiveness by hijacking actin cytoskeleton dynamics and T cell receptor vesicular trafficking
Autor: | Teck-Hui Teo, Maria-Isabel Thoulouze, Anastassia Mikhailova, Katja Brunner, Jean-Yves Tinevez, Ziv Porat, Florence Sidaner, Philippe J. Sansonetti, Julien Husson, Elisabetta Frigimelica, Fatoumata Samassa, Mariana L. Ferrari, Armelle Phalipon |
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Přispěvatelé: | Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'hydrodynamique (LadHyX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Virologie Structurale, Institut Pasteur [Paris] (IP), Flow Cytometry Unit [Rehovot, Israel], Weizmann Institute of Science [Rehovot, Israël], Proteigene [Saint Marcel], Hub d'analyse d'images - Image Analysis Hub (Platform) (IAH), Pathogénie Microbienne Moléculaire, Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), This work was supported by the French Ministry of Higher Education and Research (FS), the French Medical Research Foundation FS (FDT20170437005) and MF (SPF20121226366), the European Research Council (ERC) Grants 232798 and 339579 (PJS), the French Government's Investissement d'Avenir Program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR‐10‐LABX‐62‐IBEID), Agency of Science, Technology and Research (A*STAR), Singapore (THT), INSIS‐CNRS through the call Ingénierie translationnelle 2017' (JH), Ecole polytechnique (JH), and LabeX LaSIPS (ANR‐10‐LABX‐0040‐LaSIPS) managed by the French National Research Agency under the 'Investissements d'avenir' program (ANR‐11‐IDEX‐0003‐02) (JH)., We thank Claire Hivroz (Institut Curie, France) for kindly providing us with ζ‐GFP Jurkat cells and for helpful advices about lymphoblast experiments, Andres Alcover and Philippe Bousso (Institut Pasteur, Paris) for the kind gift of reagents and fruitful discussions. Many thanks to our PMM colleagues, Ellen Arena, Claude Parsot, Giulia Nigro, Laurie Pinaud, Ilia Belotserkovsky, and Nathalie Sauvonnet, for helpful discussions and constant support, with a particular thanks to Giulia for careful reading of the manuscript. We thank Ronan Thibaut (Institut Pasteur, Paris) for his help on some experimental set ups. We are grateful to the CRT Technology Cores (Institut Pasteur, Paris) for the use of their technical facilities and in particular to Pierre‐Henri Commère for cell sorting. We acknowledge the help of Emma Spanjaard from the Image Analysis Hub of the Institut Pasteur for the live image analysis., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0032,LaSIPS,LABORATORY FOR SYSTEMS AND ENGINEERING OF PARIS SACLAY(2010), European Project: 232798,EC:FP7:ERC,ERC-2008-AdG,HOMEOEPITH(2009), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Chaire Microbiologie et Maladies infectieuses, Tinevez, Jean-Yves, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, LABORATORY FOR SYSTEMS AND ENGINEERING OF PARIS SACLAY - - LaSIPS2010 - ANR-10-LABX-0032 - LABX - VALID, Homeostasis and rupture of the gut epithelium in the presence of commensals and pathogens - HOMEOEPITH - - EC:FP7:ERC2009-02-01 - 2013-07-31 - 232798 - VALID |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Immunological Synapses
T-Lymphocytes T cell [SDV]Life Sciences [q-bio] Immunology Receptors Antigen T-Cell Golgi Apparatus Adaptive Immunity Biology medicine.disease_cause Microbiology Cell Line Immunological synapse 03 medical and health sciences Virology Type III Secretion Systems medicine Golgi Humans Shigella cell polarisation Research Articles Dysentery Bacillary 030304 developmental biology 0303 health sciences 030306 microbiology T cell activation T-cell receptor immunological synapse T lymphocyte 16. Peace & justice Actin cytoskeleton Acquired immune system Actins Cell biology [SDV] Life Sciences [q-bio] Actin Cytoskeleton Protein Transport medicine.anatomical_structure T3SS effectors Rab proteins actin vesicular trafficking Intracellular TCR Research Article |
Zdroj: | Cellular Microbiology Cellular Microbiology, 2020, 22 (5), pp.e13166. ⟨10.1111/cmi.13166⟩ Cellular Microbiology, Wiley, 2020, 22 (5), pp.e13166. ⟨10.1111/cmi.13166⟩ |
ISSN: | 1462-5814 1462-5822 |
DOI: | 10.1111/cmi.13166⟩ |
Popis: | International audience; Strategies employed by pathogenic enteric bacteria, such as Shigella, to subvert the host adaptive immunity are not well defined. Impairment of T lymphocyte chemotaxis by blockage of polarised edge formation has been reported upon Shigella infection. However, the functional impact of Shigella on T lymphocytes remains to be determined. Here, we show that Shigella modulates CD4+ T cell F-actin dynamics and increases cell cortical stiffness. The scanning ability of T lymphocytes when encountering antigen-presenting cells (APC) is subsequently impaired resulting in decreased cell-cell contacts (or conjugates) between the two cell types, as compared with non-infected T cells. In addition, the few conjugates established between the invaded T cells and APCs display no polarised delivery and accumulation of the T cell receptor to the contact zone characterising canonical immunological synapses. This is most likely due to the targeting of intracellular vesicular trafficking by the bacterial type III secretion system (T3SS) effectors IpaJ and VirA. The collective impact of these cellular reshapings by Shigella eventually results in T cell activation dampening. Altogether, these results highlight the combined action of T3SS effectors leading to T cell defects upon Shigella infection. |
Databáze: | OpenAIRE |
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