Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages

Nature Immunology
Luigi FranchiGabriel Núñez

Abstract

Gram-negative bacteria that replicate in the cytosol of mammalian macrophages can activate a signaling pathway leading to caspase-1 cleavage and secretion of interleukin 1beta, a powerful host response factor. Ipaf, a cytosolic pattern-recognition receptor in the family of nucleotide-binding oligomerization domain-leucine-rich repeat proteins, is critical in such a response to salmonella infection, but the mechanism of how Ipaf is activated by the bacterium remains poorly understood. Here we demonstrate that salmonella strains either lacking flagellin or expressing mutant flagellin were deficient in activation of caspase-1 and in interleukin 1beta secretion, although transcription factor NF-kappaB-dependent production of interleukin 6 or the chemokine MCP-1 was unimpaired. Delivery of flagellin to the macrophage cytosol induced Ipaf-dependent activation of caspase-1 that was independent of Toll-like receptor 5, required for recognition of extracellular flagellin. In macrophages made tolerant by previous exposure to lipopolysaccharide, which abrogates activation of NF-kappaB and mitogen-activated protein kinases, salmonella infection still activated caspase-1. Thus, detection of flagellin through Ipaf induces caspase-1 activatio...Continue Reading

References

Jan 1, 1991·Chest·R L DannerJ E Parillo
Jul 1, 1984·The Journal of Experimental Medicine·A CeladaR D Schreiber
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·D HershA Zychlinsky
Apr 21, 1999·Molecular Microbiology·D E HigginsD A Portnoy
Dec 6, 2000·Microbiology and Molecular Biology Reviews : MMBR·G S Chilcott, K T Hughes
Jun 8, 2001·The Journal of Biological Chemistry·J L PoyetE S Alnemri
Jan 10, 2002·Critical Care Medicine·Michael A West, Wyrta Heagy
Jul 11, 2002·Microbes and Infection·Marina A Dobrovolskaia, Stefanie N Vogel
Oct 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mary O'RiordanDaniel A Portnoy
Dec 24, 2002·Current Opinion in Immunology·Kimberly BurnsJürg Tschopp
Mar 21, 2003·Biochemical and Biophysical Research Communications·Junya MasumotoNaohiro Inohara
May 6, 2003·Annual Review of Microbiology·Robert M Macnab
May 4, 2004·Current Biology : CB·Andrew J PerrinJohn H Brumell
Jun 11, 2004·Nature·Sanjeev MariathasanVishva M Dixit
Jul 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ramona L McCaffreyDaniel A Portnoy
Sep 30, 2004·Nature Immunology·Donald N CookDavid A Schwartz
Oct 19, 2004·Nature Immunology·Jérôme VialaRichard L Ferrero
Jan 11, 2005·Critical Reviews in Therapeutic Drug Carrier Systems·Dmitri SimbergYechezkel Barenholz
Mar 18, 2005·Annual Review of Immunology·Jenny P-Y Ting, Beckley K Davis
May 4, 2005·The Journal of Experimental Medicine·Charles A Dinarello
Jun 2, 2005·Nature Reviews. Immunology·Foo Y LiewLuke A J O'Neill
Jun 15, 2005·Annual Review of Biochemistry· InoharaGabriel Nuñez
Oct 19, 2005·The Journal of Experimental Medicine·Sanjeev MariathasanDenise M Monack
Jan 13, 2006·Nature·Thirumala-Devi KannegantiGabriel Núñez
Jan 13, 2006·Nature·Sanjeev MariathasanVishva M Dixit
Jan 18, 2006·Immunity·Daniel B Stetson, Ruslan Medzhitov
Mar 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nesrin OzörenGabriel Núñez

❮ Previous
Next ❯

Citations

Jan 9, 2007·Inflammatory Bowel Diseases·Johan Van LimbergenJack Satsangi
Mar 15, 2008·Inflammatory Bowel Diseases·Frédéric A CarvalhoArlette Darfeuille-Michaud
May 15, 2007·Immunologic Research·Chittur V Srikanth, Bobby J Cherayil
Aug 24, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Amlan BiswasKoichi S Kobayashi
Oct 16, 2009·Zeitschrift für Rheumatologie·S D Gadola
Jan 22, 2009·Apoptosis : an International Journal on Programmed Cell Death·Christian R McIntireMaya Saleh
Feb 10, 2009·Apoptosis : an International Journal on Programmed Cell Death·Fabiano Pinheiro da Silva, Victor Nizet
Mar 21, 2007·Journal of Clinical Immunology·Ken J Ishii, Shizuo Akira
Nov 21, 2007·Journal of Clinical Immunology·Shee Eun LeeJoon Haeng Rhee
Apr 8, 2010·Journal of Clinical Immunology·Russell E Vance
May 22, 2010·Journal of Clinical Immunology·Jianghong WuEmad S Alnemri
Dec 6, 2011·Current Infectious Disease Reports·John SotolongoMasayuki Fukata
Apr 27, 2010·The Proceedings of the Nutrition Society·Carolina Gómez-LlorenteAngel Gil
Nov 6, 2009·Mucosal Immunology·E C LavelleE M Creagh
Jul 6, 2012·Nature·Paras K AnandThirumala-Devi Kanneganti
Jul 8, 2008·Nature Immunology·Annett HalleDouglas T Golenbock
Mar 31, 2010·Nature Immunology·Teresa Fernandes-AlnemriEmad S Alnemri
Apr 13, 2010·Nature Immunology·Takeshi IchinoheAkiko Iwasaki
Mar 21, 2012·Nature Immunology·Luigi FranchiGabriel Núñez
Apr 20, 2012·Nature Immunology·Bernardo S Franklin, Eicke Latz
May 23, 2006·Nature Immunology·Craig R Roy, Dario S Zamboni
Nov 18, 2006·Nature Immunology·Jörg H FritzStephen E Girardin
Nov 18, 2006·Nature Immunology·Philippe J Sansonetti
Oct 24, 2007·Nature Immunology·Craig R Roy, Edward S Mocarski
Aug 21, 2013·Nature Reviews. Gastroenterology & Hepatology·Wajahat Z Mehal
May 25, 2013·Nature Reviews. Immunology·Eicke LatzAndrea Stutz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.