Integrin-mediated first signal for inflammasome activation in intestinal epithelial cells.

Abstract

How intestinal epithelial cells (IECs) recognize pathogens and activate inflammasomes at intestinal surfaces is poorly understood. We hypothesized that IECs use integrin receptors to recognize pathogens and initiate inflammation within the intestinal tract. We find that IECs infected with Yersinia enterocolitica, an enteric pathogen, use β1 integrins as pathogen recognition receptors detecting the bacterial adhesin invasin (Inv). The Inv-integrin interaction provides the first signal for NLRP3 inflammasome activation with the type three secretion system translocon providing the second signal for inflammasome activation, resulting in release of IL-18. During infection, Yersinia employs two virulence factors, YopE and YopH, to counteract Inv-mediated integrin-dependent inflammasome activation. Furthermore, NLRP3 inflammasome activation in epithelial cells requires components of the focal adhesion complex signaling pathway, focal adhesion kinase, and rac1. The binding of Inv to β1 integrins rapidly induces IL-18 mRNA expression, suggesting integrins provide a first signal for NLRP3 inflammasome activation. These data suggest integrins function as pathogen recognition receptors on IECs to rapidly induce inflammasome-derived IL-18-mediated responses.

• Authors: Josephine Thinwa, Jesus A Segovia, Santanu Bose, Peter H Dube
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 3 Pg. 1373-82 (Aug 01 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 24965773 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Adhesins, Bacterial
• Bacterial Outer Membrane Proteins
• Bacterial Toxins
• Carrier Proteins
• Inflammasomes
• Integrin alpha5beta1
• Interleukin-18
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Virulence Factors
• yopE protein, Yersinia
• invasin, Yersinia
• Protein Tyrosine Phosphatases
• yopH protein, Yersinia

Topics

• Adhesins, Bacterial (metabolism, physiology)
• Bacterial Outer Membrane Proteins (genetics, metabolism)
• Bacterial Toxins (pharmacology)
• Caco-2 Cells
• Carrier Proteins (metabolism)
• Cell Line, Tumor
• Epithelial Cells (immunology, metabolism)
• Humans
• Inflammasomes (immunology, metabolism)
• Integrin alpha5beta1 (metabolism, physiology)
• Interleukin-18 (metabolism)
• Intestinal Mucosa (immunology, metabolism, microbiology)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Protein Binding (immunology)
• Protein Tyrosine Phosphatases (deficiency, genetics)
• Signal Transduction (immunology)
• Virulence Factors (physiology)
• Yersinia enterocolitica (genetics, immunology)