Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity

Non-canonical inflammasome activation by mouse caspase-11 (or human CASPASE-4/5) is crucial for the clearance of certain gram-negative bacterial infections, but can lead to severe inflammatory damage. Factors that promote non-canonical inflammasome activation are well recognized, but less is known a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Debabrata Chowdhury, Jason C. Gardner, Abhijit Satpati, Suba Nookala, Santhosh Mukundan, Aleksey Porollo, Julio A. Landero Figueroa, Kavitha Subramanian Vignesh
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	macrophage non-canonical inflammasome zinc metallothionein innate immunity caspase-11 non-canonical inflammasome Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/86619dadcfc5411caafc7903c65e9794
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:86619dadcfc5411caafc7903c65e9794
record_format	dspace
spelling	oai:doaj.org-article:86619dadcfc5411caafc7903c65e97942021-11-12T12:12:24ZMetallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity1664-322410.3389/fimmu.2021.755961https://doaj.org/article/86619dadcfc5411caafc7903c65e97942021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.755961/fullhttps://doaj.org/toc/1664-3224Non-canonical inflammasome activation by mouse caspase-11 (or human CASPASE-4/5) is crucial for the clearance of certain gram-negative bacterial infections, but can lead to severe inflammatory damage. Factors that promote non-canonical inflammasome activation are well recognized, but less is known about the mechanisms underlying its negative regulation. Herein, we identify that the caspase-11 inflammasome in mouse and human macrophages (Mϕ) is negatively controlled by the zinc (Zn2+) regulating protein, metallothionein 3 (MT3). Upon challenge with intracellular lipopolysaccharide (iLPS), Mϕ increased MT3 expression that curtailed the activation of caspase-11 and its downstream targets caspase-1 and interleukin (IL)-1β. Mechanistically, MT3 increased intramacrophage Zn2+ to downmodulate the TRIF-IRF3-STAT1 axis that is prerequisite for caspase-11 effector function. In vivo, MT3 suppressed activation of the caspase-11 inflammasome, while caspase-11 and MT3 synergized in impairing antibacterial immunity. The present study identifies an important yin-yang relationship between the non-canonical inflammasome and MT3 in controlling inflammation and immunity to gram-negative bacteria.Debabrata ChowdhuryJason C. GardnerAbhijit SatpatiSuba NookalaSanthosh MukundanAleksey PorolloAleksey PorolloAleksey PorolloJulio A. Landero FigueroaKavitha Subramanian VigneshFrontiers Media S.A.articlemacrophagenon-canonical inflammasomezincmetallothioneininnate immunitycaspase-11 non-canonical inflammasomeImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	macrophage non-canonical inflammasome zinc metallothionein innate immunity caspase-11 non-canonical inflammasome Immunologic diseases. Allergy RC581-607
spellingShingle	macrophage non-canonical inflammasome zinc metallothionein innate immunity caspase-11 non-canonical inflammasome Immunologic diseases. Allergy RC581-607 Debabrata Chowdhury Jason C. Gardner Abhijit Satpati Suba Nookala Santhosh Mukundan Aleksey Porollo Aleksey Porollo Aleksey Porollo Julio A. Landero Figueroa Kavitha Subramanian Vignesh Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity
description	Non-canonical inflammasome activation by mouse caspase-11 (or human CASPASE-4/5) is crucial for the clearance of certain gram-negative bacterial infections, but can lead to severe inflammatory damage. Factors that promote non-canonical inflammasome activation are well recognized, but less is known about the mechanisms underlying its negative regulation. Herein, we identify that the caspase-11 inflammasome in mouse and human macrophages (Mϕ) is negatively controlled by the zinc (Zn2+) regulating protein, metallothionein 3 (MT3). Upon challenge with intracellular lipopolysaccharide (iLPS), Mϕ increased MT3 expression that curtailed the activation of caspase-11 and its downstream targets caspase-1 and interleukin (IL)-1β. Mechanistically, MT3 increased intramacrophage Zn2+ to downmodulate the TRIF-IRF3-STAT1 axis that is prerequisite for caspase-11 effector function. In vivo, MT3 suppressed activation of the caspase-11 inflammasome, while caspase-11 and MT3 synergized in impairing antibacterial immunity. The present study identifies an important yin-yang relationship between the non-canonical inflammasome and MT3 in controlling inflammation and immunity to gram-negative bacteria.
format	article
author	Debabrata Chowdhury Jason C. Gardner Abhijit Satpati Suba Nookala Santhosh Mukundan Aleksey Porollo Aleksey Porollo Aleksey Porollo Julio A. Landero Figueroa Kavitha Subramanian Vignesh
author_facet	Debabrata Chowdhury Jason C. Gardner Abhijit Satpati Suba Nookala Santhosh Mukundan Aleksey Porollo Aleksey Porollo Aleksey Porollo Julio A. Landero Figueroa Kavitha Subramanian Vignesh
author_sort	Debabrata Chowdhury
title	Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity
title_short	Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity
title_full	Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity
title_fullStr	Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity
title_full_unstemmed	Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity
title_sort	metallothionein 3-zinc axis suppresses caspase-11 inflammasome activation and impairs antibacterial immunity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/86619dadcfc5411caafc7903c65e9794
work_keys_str_mv	AT debabratachowdhury metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT jasoncgardner metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT abhijitsatpati metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT subanookala metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT santhoshmukundan metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT alekseyporollo metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT alekseyporollo metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT alekseyporollo metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT julioalanderofigueroa metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity AT kavithasubramanianvignesh metallothionein3zincaxissuppressescaspase11inflammasomeactivationandimpairsantibacterialimmunity
_version_	1718430563110486016

Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity

Ejemplares similares