Strategies that modulate inflammasomes—insights from host–pathogen interactions

Johnston, James B.; Rahman, Masmudur M.; McFadden, Grant

doi:10.1007/s00281-007-0080-5

Cited by 17 publications

(14 citation statements)

References 126 publications

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“…The MYXV-encoded PYD-containing protein M013 is required for viral pathogenicity in rabbits, and infection with the M013 knockout virus induces an exacerbated proinflammatory response that clears the virus infection (18). At the molecular level, M013 inhibits two crucial innate immune pathways regulated by NF-B and the inflammasome complexes in a species pan-specific fashion by virtue of binding independently to NF-B1/p105 and the ASC adaptor protein (18,19,35). The present study provides insights into the mechanisms by which MYXV infection is sensed and activates these two immune pathways in human myeloid cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Myxoma Virus Lacking the Pyrin-Like Protein M013 Is Sensed in Human Myeloid Cells by both NLRP3 and Multiple Toll-Like Receptors, Which Independently Activate the Inflammasome and NF-κB Innate Response Pathways

Rahman

McFadden

2011

J Virol

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The myxoma virus (MYXV)-encoded pyrin domain-containing protein M013 coregulates inflammatory responses mediated by both the inflammasome and the NF-κB pathways. Infection of human THP-1 monocytic cells with a MYXV construct deleted for the M013 gene (vMyxM013-KO), but not the parental MYXV, activates both the inflammasome and NF-κB pathways and induces a spectrum of proinflammatory cytokines and chemokines, like interleukin-1β (IL-1β), tumor necrosis factor (TNF), IL-6, and monocyte chemoattractant protein 1. Here, we report that vMyxM013-KO virus-mediated activation of inflammasomes and secretion of IL-1β are dependent on the adaptor protein ASC, caspase-1, and NLRP3 receptor. However, vMyxM013-KO virus-mediated activation of NF-κB signaling, which induces TNF secretion, was independent of ASC, caspase-1, and either the NLRP3 or AIM2 inflammasome receptors. We also report that early synthesis of pro-IL-1β in response to vMyxM013-KO infection is dependent upon the components of the inflammasome complex. Activation of the NLRP3 inflammasome and secretion of IL-1β was also dependent on the release of cathepsin B and production of reactive oxygen species (ROS). By using small interfering RNA screening, we further demonstrated that, among the RIG-I-like receptors (RLRs) and Toll-like receptors (TLRs), only TLR2, TLR6, TLR7, and TLR9 contribute to the NF-κB-dependent secretion of TNF and the inflammasome-dependent secretion of IL-1β in response to vMyxM013-KO virus infection. Additionally, we demonstrate that early triggering of the mitogen-activated protein kinase pathway by vMyxM013-KO virus infection of THP-1 cells plays a critical common upstream role in the coordinate induction of both NF-κB and inflammasome pathways. We conclude that an additional cellular sensor(s)/receptor(s) in addition to the known RLRs/TLRs plays a role in the M013 knockout virus-induced activation of NF-κB pathway signaling, but the activation of inflammasomes entirely depends on sensing by the NLRP3 receptor in response to vMyxM013-KO infection of human myeloid cells.

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Section: Discussionmentioning

confidence: 99%

Myxoma Virus Lacking the Pyrin-Like Protein M013 Is Sensed in Human Myeloid Cells by both NLRP3 and Multiple Toll-Like Receptors, Which Independently Activate the Inflammasome and NF-κB Innate Response Pathways

Rahman

McFadden

2011

J Virol

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“…Several pathogens have evolved resistance mechanism to escape the immune defence (Johnston et al, 2007). Such persistent microorganisms are the cause of chronic infections.…”

Section: Bacterial Resistance Mechanismsmentioning

confidence: 99%

“…During an acute inflammation the host actively fights invading microorganisms. This includes the inhibition of infection spread by means of physical barriers and the activation of the complement system (Johnston et al, 2007). The process is triggered by macrophage secreted cytokines (Johnston et al, 2007).…”

Section: Inflammation and Bacterial Resistance 21 Characteristics Ofmentioning

confidence: 99%

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The Impact of Macrophage Membrane Lipid Composition on Innate Immune Response Mechanisms

Schümann¹

2012

Inflammation, Chronic Diseases and Cancer - Cell and Molecular Biology, Immunology and Clinical Bases

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“…NLR-mediated inflammasome activation involves the adaptor molecule called apoptosis-associated speck-like protein containing a CARD (ASC) and CARD8 (Suzuki, Franchi et al 2007, Taniguchi andSagara 2007). NLR interaction with ASC and caspase-1 leads to autoactivation of caspase-1, and the processing of IL-1β, IL-18 and other proinflammatory mediators (Johnston, Rahman et al 2007).…”

Section: Nod-like Receptors (Nlrs)mentioning

confidence: 99%

Role of IRF6 in epithelial cell-mediated host defence and inflammation

Ramnath¹

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Strategies that modulate inflammasomes—insights from host–pathogen interactions

Cited by 17 publications

References 126 publications

Myxoma Virus Lacking the Pyrin-Like Protein M013 Is Sensed in Human Myeloid Cells by both NLRP3 and Multiple Toll-Like Receptors, Which Independently Activate the Inflammasome and NF-κB Innate Response Pathways

Myxoma Virus Lacking the Pyrin-Like Protein M013 Is Sensed in Human Myeloid Cells by both NLRP3 and Multiple Toll-Like Receptors, Which Independently Activate the Inflammasome and NF-κB Innate Response Pathways

The Impact of Macrophage Membrane Lipid Composition on Innate Immune Response Mechanisms

Role of IRF6 in epithelial cell-mediated host defence and inflammation

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