What do we know about the inflammasome in humans?

Brain Pathol. 2017 Mar;27(2):192-204. doi: 10.1111/bpa.12479.

Abstract

The inflammasome complex is part of the innate immune system, which serves to protect the host against harm from pathogens and damaged cells. It is a term first proposed by Tschopp's group in 2002, with numerous original research articles and reviews published on the topic since. There have been many types of inflammasome identified, but all result in the common pathway of activation of caspases and interleukin 1β along with possible cell death called pyroptosis. Despite a growing body of research investigating the structure and function of the inflammasome in animal models, there is still limited evidence identifying inflammasome components in human physiology and disease. In this review, we explore the molecular structure and mechanism of activation of the inflammasome with a particular focus on inflammasome complexes expressed in humans. Inflammasome components have been identified in several human peripheral and brain tissues using both in vivo and ex vivo work, and the inflammasome complex has been shown to be associated with several genetic and acquired inflammatory and neoplastic disorders. We discuss the strengths and weaknesses of the information available on the inflammasome with an emphasis on the importance of prioritizing work on human tissue. There is a huge demand for more effective treatments for a number of inflammatory and neurodegenerative diseases. Modulation of the inflammasome has been proposed as a novel treatment for several of these diseases and there are currently clinical trials ongoing to test this theory.

Keywords: NLRP; human; inflammasome; inflammasomopathies; inflammation; innate immunity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / immunology
  • Caspase 1 / metabolism
  • Caspases
  • Cell Death / genetics
  • Cell Death / immunology
  • Humans
  • Immune System
  • Inflammasomes / genetics
  • Inflammasomes / immunology
  • Inflammasomes / metabolism*
  • Inflammasomes / physiology*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Pyroptosis / genetics
  • Pyroptosis / immunology
  • Signal Transduction

Substances

  • Inflammasomes
  • Interleukin-1beta
  • Caspases
  • Caspase 1