The Shigella flexneri Type Three Secretion System Effector IpgD Inhibits T Cell Migration by Manipulating Host Phosphoinositide Metabolism
| Autor: | Elisabetta Frigimelica, Armelle Phalipon, Philippe J. Sansonetti, Daniel Scott-Algara, Katharina Nothelfer, Cristina Rodrigues, Vincenzo Di Bartolo, Christoph Konradt, Andrea Puhar, Wilmara Salgado-Pabón |
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| Přispěvatelé: | Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Cellulaire des Lymphocytes (BIOCELLY), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Dynamique des Interactions Hôte-Pathogène - Dynamics of Host-Pathogen Interactions, Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), K.N. is a fellow from the Pasteur-Paris University International Doctoral Program. A. Puhar was supported first by EMBO long-term fellowship and is presently a Marie Curie fellow. W.S.-P. is funded by the Pasteur Foundation and the Philips Foundation. P.J.S. is a HHMI Foreign Scholar. The research leading to these results has received funding from the Institut Pasteur Transversal Research Program (PTR n° 251) and from the European Community's PEOPLE Seventh Framework Program under grant agreement EIMID IAPP - PIAP-GA-2008-217768., We warmly thank C. Parsot (Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur) for very helpful discussion, M.I. Thoulouze and A. Alcover (Unité de Biologie Cellulaire des Lymphocytes, Institut Pasteur) for sharing with us their expertise in T cells, G. Chicanne and B. Payrastre (INSERM U858, I2MR, CHU Rangueil) for their expertise in PI metabolism, and M. Arpin (Institut Curie, Paris, France) for her advice on the ERM proteins. From the G5 Dynamique des Interactions Hôte-Pathogènes, Institut Pasteur, L. Audry and A. Bobard were helpful in providing tools for the injection assay, and J. Enninga for some experimental design, discussion, and critical reading of the manuscript. T. Balla (National Institute of Child Health and Human Development, National Institutes of Health [NIH]) kindly sent PLCδ1PH-RFP construct. We also thank Benoit Marteyn for his very efficient contribution in performing Shigella infection in the rabbit ileal model and processing samples for immunohistochemistry. We are also grateful to colleagues from the IMAGOPOLE platform of the Institut Pasteur. C.K. was supported by fellowships from the European Consortium PATHOGENOMICS, the Institut Pasteur Transversal Research Program n° 251, and the Howard Hughes Medical Institute (HHMI). E.F. holds a fellowship from the European Initiative for basic research in Microbiology and Infectious Diseases (EIMID Program)., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Collège de France - Chaire Microbiologie et Maladies infectieuses |
| Jazyk: | angličtina |
| Předmět: |
CD4-Positive T-Lymphocytes
Phosphatidylinositol 4 5-Diphosphate MESH: Bacterial Secretion Systems MESH: CD4-Positive T-Lymphocytes / immunology Cancer Research MESH: Phosphatidylinositols / metabolism Fluorescent Antibody Technique MESH: Phosphoric Monoester Hydrolases / metabolism Phosphatidylinositols medicine.disease_cause Shigella flexneri Type three secretion system Cell Movement Shigella Phosphorylation MESH: Shigella flexneri / metabolism Bacterial Secretion Systems MESH: Fluorescent Antibody Technique 0303 health sciences biology Effector MESH: Bacterial Proteins / metabolism MESH: DNA-Binding Proteins / metabolism MESH: CD4-Positive T-Lymphocytes / cytology DNA-Binding Proteins [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology MESH: Phosphatidylinositol 4 5-Diphosphate / deficiency Host-Pathogen Interactions Chemokines Shigellosis MESH: Chemokines / immunology Blotting Western MESH: Shigella flexneri / genetics Microbiology Cell Line 03 medical and health sciences Bacterial Proteins MESH: CD4-Positive T-Lymphocytes / metabolism Immunology and Microbiology(all) Virology medicine Humans MESH: Blotting Western Molecular Biology MESH: Cell Movement / immunology Dysentery Bacillary 030304 developmental biology MESH: Transcription Factors / metabolism MESH: Humans MESH: Phosphorylation 030306 microbiology Cell Membrane MESH: Host-Pathogen Interactions MESH: CD4-Positive T-Lymphocytes / microbiology biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease MESH: Dysentery Bacillary / metabolism Phosphoric Monoester Hydrolases MESH: Cell Line Cell culture T cell migration Parasitology MESH: Phosphatidylinositol 4 5-Diphosphate / metabolism MESH: Cell Membrane / chemistry Transcription Factors MESH: Dysentery Bacillary / genetics |
| Zdroj: | Cell Host and Microbe Cell Host and Microbe, Elsevier, 2011, 9 (4), pp.263-72. ⟨10.1016/j.chom.2011.03.010⟩ Cell Host and Microbe, 2011, 9 (4), pp.263-72. ⟨10.1016/j.chom.2011.03.010⟩ |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2011.03.010 |
| Popis: | International audience; Shigella, the Gram-negative enteroinvasive bacterium that causes shigellosis, relies on its type III secretion system (TTSS) and injected effectors to modulate host cell functions. However, consequences of the interaction between Shigella and lymphocytes have not been investigated. We show that Shigella invades activated human CD4(+) T lymphocytes. Invasion requires a functional TTSS and results in inhibition of chemokine-induced T cell migration, an effect mediated by the TTSS effector IpgD, a phosphoinositide 4-phosphatase. Remarkably, IpgD injection into bystander T cells can occur in the absence of cell invasion. Upon IpgD-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP(2)), the pool of PIP(2) at the plasma membrane is reduced, leading to dephosphorylation of the ERM proteins and their inability to relocalize at one T cell pole upon chemokine stimulus, likely affecting the formation of the polarized edge required for cell migration. These results reveal a bacterial TTSS effector-mediated strategy to impair T cell function. |
| Databáze: | OpenAIRE |
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