Reactive oxygen species regulate caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection. 2014

Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.

Enteropathogenic and enterohemorrhagic bacterial infections in humans are a severe cause of morbidity and mortality. Although NOD-like receptors (NLRs) NOD2 and NLRP3 have important roles in the generation of protective immune responses to enteric pathogens, whether there is crosstalk among NLRs to regulate immune signaling is not known. Here, we show that mice and macrophages deficient in NOD2, or the downstream adaptor RIP2, have enhanced NLRP3- and caspases-11-dependent non-canonical inflammasome activation in a mouse model of enteropathogenic Citrobacter rodentium infection. Mechanistically, NOD2 and RIP2 regulate reactive oxygen species (ROS) production. Increased ROS in Rip2-deficient macrophages subsequently enhances c-Jun N-terminal kinase (JNK) signaling resulting in increased caspase-11 expression and activation, and more non-canonical NLRP3-dependant inflammasome activation. Intriguingly, this leads to protection of the colon epithelium for up to 10 days in Rip2-deficient mice infected with C. rodentium. Our findings designate NOD2 and RIP2 as key regulators of cellular ROS homeostasis and demonstrate for the first time that ROS regulates caspase-11 expression and non-canonical NLRP3 inflammasome activation through the JNK pathway.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D003092 Colitis Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER. Colitides
D004756 Enterobacteriaceae Infections Infections with bacteria of the family ENTEROBACTERIACEAE. Enterobacterial Infections,Cronobacter Infections,Infections, Enterobacteriaceae,Infections, Enterobacterial,Cronobacter Infection,Enterobacteriaceae Infection,Enterobacterial Infection,Infection, Cronobacter,Infection, Enterobacteriaceae,Infection, Enterobacterial,Infections, Cronobacter
D005260 Female Females
D000071199 NLR Family, Pyrin Domain-Containing 3 Protein An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME. Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings

Related Publications

Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
January 2019, Cell reports,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
October 2011, Nature,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
June 2014, Annals of neurology,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
February 2020, Immunology,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
December 2018, Cell proliferation,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
October 2015, European journal of immunology,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
October 2015, European journal of immunology,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
October 2015, Nature communications,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
December 2021, The Journal of biological chemistry,
Christopher R Lupfer, and Paras K Anand, and Zhiping Liu, and Kate L Stokes, and Peter Vogel, and Mohamed Lamkanfi, and Thirumala-Devi Kanneganti
January 2017, Frontiers in immunology,
Copied contents to your clipboard!