Anthrax lethal toxin activates the inflammasome in sensitive rat macrophages.

Biochemical and Biophysical Research Communications
Zachary L NewmanMahtab Moayeri

Abstract

Anthrax lethal toxin (LT) is an important virulence factor for Bacillus anthracis. In mice, LT lyses macrophages from certain inbred strains in less than 2h by activating the Nlrp1b inflammasome and caspase-1, while macrophages from other strains remain resistant to the toxin's effects. We analyzed LT effects in toxin-sensitive and resistant rat macrophages to test if a similar pathway was involved in rat macrophage death. LT activates caspase-1 in rat macrophages from strains harboring LT-sensitive macrophages in a manner similar to that in toxin-sensitive murine macrophages. This activation of caspase-1 is dependent on proteasome activity, and sensitive macrophages are protected from LT's lytic effects by lactacystin. Proteasome inhibition also delayed the death of rats in response to LT, confirming our previous data implicating the rat Nlrp1 inflammasome in animal death. Quinidine, caspase-1 inhibitors, the cathepsin B inhibitor CA-074Me, and heat shock also protected rat macrophages from LT toxicity. These data support the existence of an active functioning LT-responsive Nlrp1 inflammasome in rat macrophages. The activation of the rat Nlrp1 inflammasome is required for LT-mediated rat macrophage lysis and contributes to ani...Continue Reading

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Citations

Dec 15, 2010·Antimicrobial Agents and Chemotherapy·Zachary L NewmanLisa M Johansen
Sep 10, 2013·PloS One·Clinton E LeysathStephen H Leppla
Apr 6, 2012·PLoS Pathogens·Jonathan L LevinsohnMahtab Moayeri
Mar 15, 2014·PLoS Pathogens·Kimberly M CirelliMahtab Moayeri
Apr 2, 2014·Trends in Microbiology·Shihui LiuStephen H Leppla
Mar 23, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Andrew W Artenstein, Steven M Opal
Dec 12, 2012·Annual Review of Immunology·Jakob von MoltkeRussell E Vance
Mar 12, 2016·Molecular Biology International·Nagendra SuryanarayanaUrmil Tuteja
Dec 31, 2011·Microbes and Infection·Mahtab MoayeriStephen H Leppla
Dec 1, 2015·Frontiers in Immunology·Allison J GreaneyMahtab Moayeri
Oct 17, 2015·Toxicon : Official Journal of the International Society on Toxinology·Suryanarayana NagendraKulanthaivel Thavachelvam
Jul 2, 2016·Applied Microbiology and Biotechnology·Nagendra SuryanarayanaVanlal Hmuaka
Jun 18, 2014·Infection and Immunity·Jana Neiman-ZenevichJeremy Mogridge
Feb 8, 2020·Nature Communications·Daniel FoxSi Ming Man
Nov 13, 2019·Innate Immunity·Catherine E VrentasMahtab Moayeri
Nov 20, 2012·Toxins·Stephanie AscoughDaniel M Altmann
Mar 25, 2017·Frontiers in Cellular Neuroscience·Limin SongYou Shang
Feb 7, 2021·International Journal of Molecular Sciences·Miranda Sin-Man TsangChun Kwok Wong
May 22, 2019·Microbiology Spectrum·Monika Ehling-SchulzTheresa M Koehler

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