The adhesive protein invasin of Yersinia pseudotuberculosis induces neutrophil extracellular traps via β1 integrins

Yersinia pseudotuberculosis adhesive protein invasin is crucial for the bacteria to cross the intestine epithelium by binding to beta 1 integrins on M-cells and gaining access to the underlying tissues. After the crossing invasin can bind to beta 1 integrins on other cell surfaces, however effector proteins delivered by the type HI secretion system Y. pseudotuberculosis efficiently inhibit potential immune responses induced by this interaction. Here, we use mutant Y pseudotuberculosis strains lacking the type III secretion system and additionally invasin-expressing Escherichia colt to analyze neutrophil responses towards invasin. Our data reveals that invasin induces production of reactive oxygen species and release of chromatin into the extracellular milieu, which we confirmed to be neutrophil extracellular traps by immunofluorescence microscopy. This was mediated through beta 1 integrins and was dependent on both the production of reactive oxygen species and signaling through phosphoinositide 3-kinase. We therefore have gained insight into a potential role of integrins in inflammation and infection clearance that has not previously been described, suggesting that targeting of beta 1 integrins could be utilized as an adjunctive therapy against yersiniosis. (C) 2015 The Authors. Published by Elsevier Masson SAS on behalf of Institut Pasteur.