PI5P Triggers ICAM-1 Degradation in Shigella Infected Cells, Thus Dampening Immune Cell Recruitment

• Published in: Cell reports (Cambridge) Vol. 14; no. 4; pp. 750 - 759
• Main Authors: Boal, Frédéric, Puhar, Andrea, Xuereb, Jean-Marie, Kunduzova, Oksana, Sansonetti, Philippe J., Payrastre, Bernard, Tronchère, Hélène
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.02.2016; Elsevier
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; HT29 Cells; Humans; Immune Evasion; Infectious Diseases; infektionssjukdomar; Intercellular Adhesion Molecule-1 - metabolism; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Mice; Neutrophil Activation; Neutrophils - immunology; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Proteolysis; Shigella flexneri - immunology; Shigella flexneri - pathogenicity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.12.079

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. [Display omitted] •Shigella’s meta-effector IpgD is responsible for the internalization of ICAM-1•Internalized ICAM-1 is targeted for degradation in a PI5P-dependent manner•Neutrophil recruitment to infected intestinal cells is reduced in vitro and in vivo•ICAM-1 internalization contributes to the immune evasion mechanism used by Shigella Boal et al. show that Shigella’s meta-effector IpgD triggers, via PI5P production, the internalization and degradation of the adhesion molecule ICAM-1 in infected intestinal cells, thereby reducing neutrophil recruitment both in vitro and in vivo. Their results uncover a strategy of immune evasion used by this pathogen.