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: Frédéric Boal, Andrea Puhar, Jean-Marie Xuereb, Oksana Kunduzova, Philippe J Sansonetti, Bernard Payrastre, Hélène Tronchère
• Journal: Cell reports (Cell Rep) Vol. 14 Issue 4 Pg. 750-759 (Feb 02 2016) ISSN: 2211-1247 [Electronic] United States
• PMID: 26776508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Proteins
• Intercellular Adhesion Molecule-1
• Phosphotransferases (Alcohol Group Acceptor)
• IpgD protein, Shigella flexneri
• Phosphoric Monoester Hydrolases

Topics

• Animals
• Bacterial Proteins (genetics, metabolism)
• HT29 Cells
• Humans
• Immune Evasion
• Intercellular Adhesion Molecule-1 (metabolism)
• Intestinal Mucosa (metabolism, microbiology)
• Mice
• Neutrophil Activation
• Neutrophils (immunology)
• Phosphoric Monoester Hydrolases (genetics, metabolism)
• Phosphotransferases (Alcohol Group Acceptor) (metabolism)
• Proteolysis
• Shigella flexneri (immunology, pathogenicity)