title: The Shigella flexneri type three secretion system effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism.
abstract: 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.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France.
authors.forename: Christoph
authors.initials: C
authors.lastname: Konradt
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Frigimelica
authors.forename: Katharina
authors.initials: K
authors.lastname: Nothelfer
authors.forename: Andrea
authors.initials: A
authors.lastname: Puhar
authors.forename: Wilmara
authors.initials: W
authors.lastname: Salgado-Pabon
authors.forename: Vincenzo
authors.initials: V
authors.lastname: di Bartolo
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
authors.forename: Cristina D
authors.initials: CD
authors.lastname: Rodrigues
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: Armelle
authors.initials: A
authors.lastname: Phalipon
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D054884:Host-Pathogen Interactions; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000172:deficiency / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D018925:Chemokines; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D014157:Transcription Factors; C425774:IpgD protein, Shigella flexneri; D010744:Phosphoric Monoester Hydrolases