The role of the microbiome and the NLRP3 inflammasome in the gut and lung

J Leukoc Biol. 2020 Sep;108(3):925-935. doi: 10.1002/JLB.3MR0720-472RR. Epub 2020 Aug 17.

Abstract

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut-lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut-lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.

Keywords: NLRP3 inflammasome; gut; lung; microbiome; microbiota.

Publication types

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

MeSH terms

  • Aging / immunology
  • Air Pollutants / toxicity
  • Animals
  • Asthma / immunology
  • Cigarette Smoking / immunology
  • Colitis / immunology
  • Colitis / microbiology
  • Colitis / therapy
  • Dysbiosis / immunology
  • Fecal Microbiota Transplantation
  • Furans
  • Gastrointestinal Microbiome / immunology*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Indenes
  • Inflammasomes / immunology*
  • Inflammation / immunology*
  • Intestines / immunology*
  • Lung / immunology*
  • Mice
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein / deficiency
  • NLR Family, Pyrin Domain-Containing 3 Protein / physiology*
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Viral / immunology
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Specific Pathogen-Free Organisms
  • Sulfonamides
  • Sulfones / pharmacology
  • Symbiosis

Substances

  • Air Pollutants
  • Furans
  • Heterocyclic Compounds, 4 or More Rings
  • Indenes
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Sulfonamides
  • Sulfones
  • N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide