The role of NLRs and TLRs in the activation of the inflammasome

Abstract

Background: Interleukin-1β is one of the most important pro-inflammatory cytokines. In contrast to other cytokines, activation of IL-1β requires processing from an inactive precursor by the cysteine protease caspase-1. Caspase-1 forms a protein platform called the inflammasome, together with proteins of the nucleotide-binding oligomerization domain-like receptor (NLR) family. Objective/methods: A review of literature investigating the stimulation of IL-1β production by microbial pathogens and their components. Results/conclusions: To produce IL-1β, macrophages need a double stimulation with Toll like receptor (TLR) ligands that induce gene transcription, and NLR agonists (such as ATP or muramyl dipeptide (MDP)) that activate the inflammasome. Monocytes can release active IL-1β upon stimulation with TLR ligands alone. This probably represents an adaptation of each cell type to its environment.

Keywords::

• caspase-1
• cytokines
• host defense inflammasome
• NLRs
• TLRs

Notes