title: PI5P Triggers ICAM-1 Degradation in Shigella Infected Cells, Thus Dampening Immune Cell Recruitment.
abstract: Shigella flexneri, the pathogen responsible for bacillary dysentery, has evolved multiple strategies to control the inflammatory response. Here, we show that Shigella subverts the subcellular trafficking of the intercellular adhesion molecule-1 (ICAM-1), a key molecule in immune cell recruitment, in a mechanism dependent on the injected bacterial enzyme IpgD and its product, the lipid mediator PI5P. Overexpression of IpgD, but not a phosphatase dead mutant, induced the internalization and the degradation of ICAM-1 in intestinal epithelial cells. Remarkably, addition of permeant PI5P reproduced IpgD effects and led to the inhibition of neutrophil recruitment. Finally, these results were confirmed in an in vivo model of Shigella infection where IpgD-dependent ICAM-1 internalization reduced neutrophil adhesion. In conclusion, we describe here an immune evasion mechanism used by the pathogen Shigella to divert the host cell trafficking machinery in order to reduce immune cell recruitment.
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boal
authors.affiliation: INSERM U1202, Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75724 Paris Cedex 15, France; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR) and Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Puhar
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Xuereb
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Oksana
authors.initials: O
authors.lastname: Kunduzova
authors.affiliation: INSERM U1202, Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75724 Paris Cedex 15, France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France; CHU de Toulouse, Laboratoire d'Hématologie, 31059 Toulouse Cedex 03, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France. Electronic address: helene.tronchere@inserm.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Tronchère
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D057131:Immune Evasion; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D059748:Proteolysis; D012763:Shigella flexneri / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D018799:Intercellular Adhesion Molecule-1; D017853:Phosphotransferases (Alcohol Group Acceptor); C425774:IpgD protein, Shigella flexneri; D010744:Phosphoric Monoester Hydrolases