The NLRC4 inflammasome requires IRF8-dependent production of NAIPs.

Thirumala-Devi Kanneganti,Rajendra Karki,Ein Lee

doi:10.15698/cst2018.06.141

Abstract

Activation of the NLRC4 inflammasome is crucial for defense against bacterial species that have flagellin or the type III secretion system (T3SS). We have discovered the role of interferon regulatory factor 8 (IRF8) in mediating NLRC4 inflammasome activation. IRF8 is required for the transcription of genes encoding NAIPs, thereby enabling cellular detection of flagellin or T3SS proteins. In vivo, IRF8 is important for NLRC4 inflammasome-dependent cytokine production, bacterial clearance, and ultimately, host survival. By introducing IRF8 as a player in inflammasome regulation, our study provides a new perspective on that process.

Highlights

Inflammasomes orchestrate cellular responses to pathogen- or danger-associated molecular patterns by controlling the activation of caspase-1
We have discovered the role of interferon regulatory factor 8 (IRF8) in mediating NLRC4 inflammasome activation
We have demonstrated for the first time that interferon regulatory factor 8 (IRF8) is a critical regulator of NLRC4 inflammasome activation for host defense against Gram-negative bacteria

Summary

Introduction

Inflammasomes orchestrate cellular responses to pathogen- or danger-associated molecular patterns by controlling the activation of caspase-1. The NLRC4 inflammasome requires IRF8-dependent production of NAIPs * Corresponding Author: Thirumala-Devi Kanneganti, Department of Immunology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA; E-mail: thirumala-devi.kanneganti@stjude.org Activation of the NLRC4 inflammasome is crucial for defense against bacterial species that have flagellin or the type III secretion system (T3SS).

Results

Conclusion