Inflammasomes in the Gut Mucosal Homeostasis

Abstract

Inflammasomes are critical checkpoints in inflammation. The activation of inflammasome can cause a series of inflammatory responses including maturation of interleukin (IL)-1β and IL-18 and a specialized form of cell death called pyroptosis. Since its identification in the early 2000s, inflammasomes have been implicated to play multifaceted roles in varied pathological and physiological conditions, especially in the mucosal compartments including the gut. Maintaining gut mucosal homeostasis has always been a remarkable challenge for the host due to both the vast mucosal surface that is exposed to the outside and the enormous amount of local microbiota. To accomplish this challenge, the host mounts a constant dynamic low-grade inflammatory response (physiological inflammation) in coping with insults of microbes in the intestine. This book chapter aims to summarize the current knowledge of how inflammasomes contribute to gut mucosal homeostasis.

Bacteroides fragilis Strain ZY-312 Defense against Cronobacter sakazakii-Induced Necrotizing Enterocolitis In Vitro and in a Neonatal Rat Model

“…In this study, we have shown for the first time that C. sakazakii not only induces apoptosis but also elicits pyroptosis, triggered by caspase-1 activation via inflammasomes (39). The premature human gut is notable for displaying increased expression of various proinflammatory cytokines.…”

“…Inflammatory responses are activated by inflammasomes (multiprotein oligomers), which are responsible for a more robust immune response to microbial pathogens and which promote the activation/maturation of inflammatory caspase-1 and proinflammatory cytokines such as IL-1β (39). Proteus mirabilis, through the NLRP3 inflammasome, can contribute to dextran sulfate sodium-induced colitis, indicating that disease outcomes are affected by the various commensal microbiota present in the intestine.…”

Low NLRP3 expression predicts a better prognosis of colorectal cancer

“…Although physiological inflammation was beneficial to the intestine, overwhelming inflammatory microenvironment and excessive inflammatory cytokines can ultimately prompt colonic tumorigenesis [29,30]. As a critical initiator of inflammation, NLRP3 inflammasomes play a critical role in regulating the inflammatory microenvironment by inflecting innate immune responses, recruiting immunocytes, mediating cell deaths, and stabilizing gut microbiota [31,32]. The specific effect varies with the signal pathways involved.…”

<p>In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends</p>

“…[24][25][26][27] In addition, while it appears that there have been correlations noted between the microbiome of the gut and inflammasome activation, solid links between the skin microbiome and inflammasome activation or suppression are lacking. 28,29 The activated nod-like receptor proteins, or NLRPs, create circular Inflammasome oligomers, Figure 1. The NLRPs are comprised of three key molecular components that include 1) Nucleotide-binding domain and Leucinerich repeat Receptors (NLR), 2) Apoptosis-associated Speck-like protein (ASC), and 3) inactive Caspase-1 (Pro-Caspase-1).…”