How Inflammasomes Inform Adaptive Immunity

Abstract

An immune response consists of a finely orchestrated interplay between initial recognition of potential microbial threats by the innate immune system and subsequent licensed adaptive immune neutralization. The initial recognition integrates environmental cues derived from pathogen-associated molecular patterns and cell-intrinsic damage-associated molecular patterns to contextualize the insult and inform a tailored adaptive response via T and B lymphocytes. While there are much data to support the role of transcriptional responses downstream of pattern recognition receptors in informing the adaptive immune response, markedly less attention has been paid to the role of post-translational responses to pathogen-associated molecular pattern and damage-associated molecular pattern recognition by the innate immune system, and how this may influence adaptive immunity. A well-characterized post-translational consequence of pattern recognition receptor signaling is the assembly of a multimeric signaling platform, termed the inflammasome, by members of the nucleotide-binding oligomerization domain (Nod), leucine-rich repeat-containing receptors (NLRs), and pyrin and HIN domain (PYHIN) families. Inflammasomes assemble in response to cytosolic perturbations, such as mitochondrial dysfunction and aberrant ion fluxes in the case of the canonical NLRP3 inflammasome or the presence of bacterial lipopolysaccharides in the case of the non-canonical inflammasome. Assembly of the inflammasome allows for the cleavage and activation of inflammatory caspases. These activated inflammatory caspases in turn cleave pro-form inflammatory cytokines into their mature bioactive species and lead to unconventional protein secretion and lytic cell death. In this review, we discuss evidence for inflammasome-mediated instruction and contextualization of infectious and sterile agents to the adaptive immune system.