NAIP-NLRC4 Inflammasomes Coordinate Intestinal Epithelial Cell Expulsion with Eicosanoid and IL-18 Release via Activation of Caspase-1 and -8

Isabella Rauch, Katherine A. Deets, Daisy X. Ji, Jakob von Moltke, Jeannette L. Tenthorey, Angus Y. Lee, Naomi H. Philip, Janelle S. Ayres, Igor E. Brodsky, Karsten Gronert, Russell E. Vance

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Intestinal epithelial cells (IECs) form a critical barrier against pathogen invasion. By generation of mice in which inflammasome expression is restricted to IECs, we describe a coordinated epithelium-intrinsic inflammasome response in vivo. This response was sufficient to protect against Salmonella tissue invasion and involved a previously reported IEC expulsion that was coordinated with lipid mediator and cytokine production and lytic IEC death. Excessive inflammasome activation in IECs was sufficient to result in diarrhea and pathology. Experiments with IEC organoids demonstrated that IEC expulsion did not require other cell types. IEC expulsion was accompanied by a major actin rearrangement in neighboring cells that maintained epithelium integrity but did not absolutely require Caspase-1 or Gasdermin D. Analysis of Casp1–/–Casp8–/– mice revealed a functional Caspase-8 inflammasome in vivo. Thus, a coordinated IEC-intrinsic, Caspase-1 and -8 inflammasome response plays a key role in intestinal immune defense and pathology.

Original languageEnglish (US)
Pages (from-to)649-659
Number of pages11
JournalImmunity
Volume46
Issue number4
DOIs
StatePublished - Apr 18 2017
Externally publishedYes

Keywords

  • ASC
  • Caspase-1
  • Caspase-8
  • expulsion
  • extrusion
  • inflammasome
  • intestinal epithelial cell
  • Naip
  • Nlrc4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Rauch, I., Deets, K. A., Ji, D. X., von Moltke, J., Tenthorey, J. L., Lee, A. Y., Philip, N. H., Ayres, J. S., Brodsky, I. E., Gronert, K., & Vance, R. E. (2017). NAIP-NLRC4 Inflammasomes Coordinate Intestinal Epithelial Cell Expulsion with Eicosanoid and IL-18 Release via Activation of Caspase-1 and -8. Immunity, 46(4), 649-659. https://doi.org/10.1016/j.immuni.2017.03.016