Inflammasomes and intestinal homeostasis: regulating and connecting infection, inflammation and the microbiota.

Inflammasomes are large cytosolic protein complexes that detect infection and stress-associated signals and promote immediate inflammatory responses. In the intestine, activation of the inflammasome leads to an inflammatory response that is important for controlling enteric infections but can also result in pathological tissue damage. Recent studies have suggested that the inflammasome also regulates intestinal homeostasis through its effects on the intestinal microbiota. Notably, many conflicting studies have been published regarding the effect of inflammasome deficiencies on intestinal homeostasis. Here, we attempt to reconcile these contrasting data by highlighting the many ways that the inflammasome contributes to intestinal homeostasis and pathology and exploring the potential role of alterations in the microbiota in these conflicting studies.

[1]  E. Elinav,et al.  NLRP6 Inflammasome Orchestrates the Colonic Host-Microbial Interface by Regulating Goblet Cell Mucus Secretion , 2014, Cell.

[2]  Zihai Li,et al.  Inflammasome activation plays an important role in the development of spontaneous colitis , 2016 .

[3]  S. Nordlander,et al.  NLRC4 expression in intestinal epithelial cells mediates protection against an enteric pathogen , 2013, Mucosal Immunology.

[4]  K. Maloy,et al.  Nlrp3 Activation in the Intestinal Epithelium Protects against a Mucosal Pathogen , 2013, Mucosal Immunology.

[5]  R. Flavell,et al.  Interactions between Nod-Like Receptors and Intestinal Bacteria , 2013, Front. Immunol..

[6]  M. Idzko,et al.  The Nlrp3 inflammasome regulates acute graft-versus-host disease , 2013, The Journal of experimental medicine.

[7]  D. Powell,et al.  Cytoplasmic LPS Activates Caspase-11: Implications in TLR4-Independent Endotoxic Shock , 2013, Science.

[8]  M. T. Wong,et al.  Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4 , 2013, Science.

[9]  E. Elinav,et al.  Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer , 2013, Proceedings of the National Academy of Sciences.

[10]  Daniel E. Zak,et al.  Caspase-11 Protects Against Bacteria That Escape the Vacuole , 2013, Science.

[11]  H. Lehr,et al.  Protective and Aggravating Effects of Nlrp3 Inflammasome Activation in IBD Models: Influence of Genetic and Environmental Factors , 2012, Digestive Diseases.

[12]  R. Flavell,et al.  Life, death, and miracles: Th17 cells in the intestine , 2012, European journal of immunology.

[13]  Francis J. Huber,et al.  IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine , 2012, Nature.

[14]  E. Elinav,et al.  Inflammasomes: far beyond inflammation , 2012, Nature Immunology.

[15]  Richard A. Flavell,et al.  Inflammasomes in health and disease , 2012, Nature.

[16]  J. Sauer,et al.  Innate immune pathways triggered by Listeria monocytogenes and their role in the induction of cell-mediated immunity. , 2012, Advances in immunology.

[17]  Jinfeng Liu,et al.  Non-canonical inflammasome activation targets caspase-11 , 2011, Nature.

[18]  K. Fitzgerald,et al.  The PYHIN protein family as mediators of host defenses , 2011, Immunological reviews.

[19]  A. Aderem,et al.  Caspase‐1‐induced pyroptotic cell death , 2011, Immunological Reviews.

[20]  M. Gale,et al.  RIG-I Like Receptors in Antiviral Immunity and Therapeutic Applications , 2011, Viruses.

[21]  Richard A. Flavell,et al.  NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis , 2011, Cell.

[22]  Y. Wan,et al.  Memory/effector (CD45RBlo) CD4 T cells are controlled directly by IL-10 and cause IL-22–dependent intestinal pathology , 2011, The Journal of experimental medicine.

[23]  E. Miao,et al.  Salmonella and Caspase-1: A complex Interplay of Detection and Evasion , 2011, Front. Microbio..

[24]  E. Elinav,et al.  Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4 , 2010, Proceedings of the National Academy of Sciences.

[25]  F. Marincola,et al.  MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18 , 2010, The Journal of experimental medicine.

[26]  F. Sutterwala,et al.  A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system. , 2010, Cell host & microbe.

[27]  J. Tschopp,et al.  Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome , 2010, Gut.

[28]  M. Kastan,et al.  The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. , 2010, Immunity.

[29]  N. Beauchemin,et al.  Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. , 2010, Immunity.

[30]  J. Tschopp,et al.  The Inflammasomes , 2010, Cell.

[31]  A. Murphy,et al.  Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. , 2008, Immunity.

[32]  Lois J. Maltais,et al.  The NLR gene family: a standard nomenclature. , 2008, Immunity.

[33]  A. Murphy,et al.  Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. , 2007, Immunity.

[34]  T. Ma,et al.  IL-1β Causes an Increase in Intestinal Epithelial Tight Junction Permeability1 , 2007, The Journal of Immunology.

[35]  H. Lehr,et al.  The ICE Inhibitor Pralnacasan Prevents DSS-Induced Colitis in C57BL/6 Mice and Suppresses IP-10 mRNA but Not TNF-α mRNA Expression , 2007, Digestive Diseases and Sciences.

[36]  T. Pizarro,et al.  Commentary: The role of the IL‐18 system and other members of the IL‐1R/TLR superfamily in innate mucosal immunity and the pathogenesis of inflammatory bowel disease: friend or foe? , 2004, European journal of immunology.

[37]  H. Lehr,et al.  The Interleukin-1β-Converting Enzyme Inhibitor Pralnacasan Reduces Dextran Sulfate Sodium-Induced Murine Colitis and T Helper 1 T-Cell Activation , 2004, Journal of Pharmacology and Experimental Therapeutics.

[38]  H. Lehr,et al.  The interleukin-1 beta-converting enzyme inhibitor pralnacasan reduces dextran sulfate sodium-induced murine colitis and T helper 1 T-cell activation. , 2004, The Journal of pharmacology and experimental therapeutics.

[39]  S. Akira,et al.  Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice. , 2003, Scandinavian journal of gastroenterology.

[40]  J. Derry,et al.  Inflammation and Inflammatory Bowel Disease , 2022 .

[41]  G. Fantuzzi,et al.  IL-1β-converting enzyme (caspase-1) in intestinal inflammation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[42]  G. Fantuzzi,et al.  IL-1 beta -converting enzyme (caspase-1) in intestinal inflammation. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[43]  R. Sartor,et al.  Cytokines in intestinal inflammation: pathophysiological and clinical considerations. , 1994, Gastroenterology.