Cytosolic Double-Stranded RNA Activates the NLRP3 Inflammasome via MAVS-Induced Membrane Permeabilization and K+ Efflux

Franchi, Luigi; Eigenbrod, Tatjana; Muñoz-Planillo, Raúl; Ozkurede, Ulas; Kim, Yun Gi; Chakrabarti, Arindam; Gale, Michael; Silverman, Robert H.; Colonna, Marco; Akira, Shizuo; Núñez, Gabriel

doi:10.4049/jimmunol.1400582

Cited by 145 publications

(139 citation statements)

References 60 publications

(76 reference statements)

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“…PKR, a dsRNA-activated protein kinase, recently was implicated as a common regulator of inflammasome activation by E. coli RNA and polyinosinicpolycytidylic acid, as well as by a variety of other stimuli, including ATP, monosodium urate crystals, cytosolic DNA, or infection with E. coli and Salmonella (60). However, the general role of PKR for caspase-1 cleavage could not be confirmed in subsequent studies by other groups (61)(62)(63). The reason for these discrepancies remains elusive, and further studies are needed to clarify the contribution of PKR to inflammasome activation.…”

Section: Inflammasome Activation By Bacterial Rnamentioning

confidence: 53%

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses

Eigenbrod

Dalpke

2015

The Journal of Immunology

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Although DNA of bacterial and viral origin, as well as viral RNA, have been intensively studied as triggers of innate immune responses, the stimulatory properties of bacterial RNA and its role during infections have just begun to be deciphered. Bacterial RNA is a strong inducer of type I IFN and NF-κB–dependent cytokines, and it also can activate the Nlrp3 inflammasome. In this review, we focus on the receptors and signaling pathways involved in innate immune activation by bacterial RNA and analyze the physiological relevance of bacterial RNA recognition during infections. Furthermore, we present the concept that RNA modifications can impair RNA-dependent immune activation. RNA modifications differ between eukaryotes and prokaryotes; thus, they can serve to define the innate pattern that is recognized. In this regard, we discuss the role of ribose 2′-O-methylation as a potential immune-escape mechanism.

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Section: Inflammasome Activation By Bacterial Rnamentioning

confidence: 53%

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses

Eigenbrod

Dalpke

2015

The Journal of Immunology

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“…This CARD-CARD interaction results in the dimerisation of MAVS in the mitochondria to form a protein complex called the MAVS signalosome, which enables the activation of NF-jB and the production of type I interferon (IFN). Once the innate immune system has been activated, it elicits the secretion of cytokines and chemokines, which subsequently induce the expression of adhesion molecules and costimulatory molecules to further activate the adaptive immune response [4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Inflammasomes and its importance in viral infections

León-Juárez²,

et al. 2016

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A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1. The inflammasome operates as a platform for caspase-1 activation, resulting in caspase-1-dependent proteolytic maturation and secretion of interleukin (IL)-1b and IL-18. This, in turn, activates the expression of other immune genes and facilitates lymphocyte recruitment to the site of primary infection, thereby controlling invading pathogens. Moreover, inflammasomes counter viral replication and remove infected immune cells through an inflammatory cell death, program termed as pyroptosis. As a countermeasure, viral pathogens have evolved virulence factors to antagonise inflammasome pathways. In this review, we discuss the role of inflammasomes in sensing viral infection as well as the evasion strategies that viruses have developed to evade inflammasome-dependent immune responses. This information summarises our understanding of host defence mechanisms against viruses and highlights research areas that can provide new approaches to interfere in the pathogenesis of viral diseases.

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“…Others have shown that the MAVS protein complex is required for optimal NLRP3 recruitment and inflammasome activity (Franchi et al, 2014;Park et al, 2013;Subramanian et al, 2013). Other members of this antiviral complex are recruited to the ER-mitochondria interface to fine-tune MAVS-NLRP3 signaling, including stimulator of IFN genes (STING) ((Abdul-Sater et al, 2013;Abe and Barber, 2014), Figure 2).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

From dysfunctional endoplasmic reticulum-mitochondria coupling to neurodegeneration

Erpapazoglou

Mouton-Liger

Corti

2017

Neurochemistry International

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Over the last years, contact sites between the endoplasmic reticulum (ER) and mitochondria have attracted great attention in the study of cell homeostasis and dysfunction, especially in the context of neurodegenerative disorders. This is largely due to the critical involvement of this subcellular compartment in a plethora of vital cellular functions: Ca 2+ homeostasis, mitochondrial dynamics, transport, bioenergetics and turnover, ER stress, apoptotic signaling and inflammation. An increasing number of disease-associated proteins have been reported to physically associate with the ERmitochondria interface, and cause structural and/or functional perturbations of this compartment. In the present review, we summarize current knowledge about the architecture and functions of the ER-mitochondria contact sites, and the consequences of their alteration in different neurodegenerative disorders. Special emphasis is placed on the caveats and difficulties in defining the nature and origin of the highlighted defects in ER-mitochondria communication, and their exact contribution to the neurodegenerative process.

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Cytosolic Double-Stranded RNA Activates the NLRP3 Inflammasome via MAVS-Induced Membrane Permeabilization and K+ Efflux

Cited by 145 publications

References 60 publications

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses

Inflammasomes and its importance in viral infections

From dysfunctional endoplasmic reticulum-mitochondria coupling to neurodegeneration

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