Regulation and functions of NLRP3 inflammasome during influenza virus infection

Kuriakose, Teneema; Kanneganti, Thirumala‐Devi

doi:10.1016/j.molimm.2017.01.023

Cited by 67 publications

(63 citation statements)

References 79 publications

(188 reference statements)

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“…To characterize the bat NLRP3 in response to virus infection, LPS-primed iMACs were infected with H1N1 influenza A virus (IAV), strain A/NWS/33. It is a negative-sense single-stranded RNA (−ssRNA) virus, known to activate the NLRP3 inflammasome 27 . All bat NLRP3 isoforms were significantly less responsive to IAV infection, while viral titres from supernatants were not affected ( Fig.…”

Section: Nlrp3-mediated Inflammation Is Dampened In Bat Immune Cells mentioning

confidence: 99%

“…NLR family pyrin domain containing 3 (NLRP3) is an important sensor that recognizes both cellular stresses (such as extracellular adenosine triphosphate (ATP), mitochondrial damage and oxidized DNA) [24][25][26] and viral or bacterial infections 27,28 . NLRP3-mediated inflammation has been causally linked to aging and multiple agerelated chronic diseases 29,30 .…”

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Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host

et al. 2019

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ResultsActivation of NLRP3 inflammasome is dampened in bat primary immune cells. Following priming (signal 1) and activation (signal 2), NLRP3 triggers assembly of the diffuse cytosolic apoptosis-associated speck-like protein containing a CARD (ASC) protein to form ASC specks 40 . These then recruit and activate caspase-1 to promote inflammatory cell death via pyroptosis and cleavage/secretion of the potent pro-inflammatory cytokine interleukin-1β (IL-1β) ( Fig. 1a).Bats are special in their ability to host emerging viruses. As the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. It is currently unclear whether these unique features are interlinked. The important inflammasome sensor, NLR family pyrin domain containing 3 (NLRP3), has been linked to both viral-induced and age-related inflammation. Here, we report significantly dampened activation of the NLRP3 inflammasome in bat primary immune cells compared to human or mouse counterparts. Lower induction of apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and secretion of interleukin-1β in response to both 'sterile' stimuli and infection with multiple zoonotic viruses including influenza A virus (−single-stranded (ss) RNA), Melaka virus (PRV3M, double-stranded RNA) andMiddle East respiratory syndrome coronavirus (+ssRNA) was observed. Importantly, this reduction of inflammation had no impact on the overall viral loads. We identified dampened transcriptional priming, a novel splice variant and an altered leucine-rich repeat domain of bat NLRP3 as the cause. Our results elucidate an important mechanism through which bats dampen inflammation with implications for longevity and unique viral reservoir status.

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Section: Nlrp3-mediated Inflammation Is Dampened In Bat Immune Cells mentioning

confidence: 99%

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confidence: 99%

Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host

et al. 2019

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“…inflammasome activation [79,82]. It was shown that the M2del29-31 mutant of the influenza virus (lacking amino acids 29-31 from the transmembrane region of the M2 protein) completely failed to stimulate inflammasome activation and release of IL-1β or IL-18 from BMM and BMDCs [79].…”

Section: By Altering Ionic Concentrations Of Intracellular Compartmenmentioning

confidence: 99%

Viroporins and inflammasomes: A key to understand virus-induced inflammation

Farag

Breitinger

Azizi

2020

The International Journal of Biochemistry & Cell Biology

110

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J o u r n a l P r e -p r o o f Highlights  The article provides a summary on cellular receptors involved in virus immunity.  It presents an overview of the current understanding of inflammasomes complex activation, comparing its different types with special focus on NLRP3.  The article summarizes key findings on viroporins, a novel class of viral proteins and their role in the virus life cycle and host cell interactions.  The article sheds the light on the correlation between viroporins and inflammasomes activation and their possible contribution to aggravated inflammatory cytokines production.  The article proposes targeting inflammasomes in combination with viroporin inhibitors in virus-induced disease as an emerging attractive therapeutic option. Abstract Viroporins are virus encoded proteins that alter membrane permeability and can trigger subsequent cellular signals. Oligomerization of viroporin subunits results in formation of a hydrophilic pore which facilitates ion transport across host cell membranes. These viral channel proteins may be involved in different stages of the virus infection cycle. J o u r n a l P r e -p r o o f List of abbreviationsAIM Absent in melanoma ASC Apoptosis-associated speck-like protein containing a carboxy-terminal CARD ATP Adenosine triphosphate BMDC Bone marrow derived dendritic cells BMM Bone marrow derived macrophages CARD Caspase activation and recruitment domain CD Cluster of differentiation CoV Coronavirus CSFV Classical swine fever virus DAMPs Danger associated molecular patterns DC Dendritic cells EMCV Encephalomyocarditis virus HCV Hepatitis C virus HIV Human immune deficiency virus LPS Lipopolysaccharide LRR Leucine rich repeats MAL MyD88-adaptor-like MAM Mitochondrial-associated membrane MAVS Mitochondrial antiviral signaling protein MDA5 Melanoma differentiation-associated protein 5 MERS Middle East respiratory syndrome-related coronavirus MHC Major histocompatibility complex J o u r n a l P r e -p r o o f MSU Monosodium urate MyD88 Myeloid differentiation primary response 88 NADPH Nicotinamide adenine dinucleotide phosphate NALP NACHT, LRR and PYD domains-containing protein NFκB Nuclear factor kappa b NLR Nucleotide-binding domain, leucine-rich repeat NLRP3 NLR family, pyrin domain containing 3 Nod Nucleotide oligomerization domain PAMP Pathogen associated molecular patterns PRR Pattern recognition receptors PYD Pyrin domain RIG-1 Retinoic acid-inducible gene I RLR RIG-1 like receptor ROS Reactive Oxygen species RSV Respiratory syncytial virus

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“…Also, a recent study using NLRP3 inhibitor reported that NLRP3 plays a protective role in the early stage of influenza infection, but a detrimental role in the late stage through increased cytokine production and lung cellular infiltrates (39). The NLRP3 inflammasome can be activated by many conditions including a variety of pathogen-and damage-associated molecular patterns and different stresses (45)(46)(47). Therefore, a difference in viral dose, virus production, course of infection, animal facility, and the sex of mice could lead to different results.…”

Section: Aim2 Deficiency Provides Protection Against Iav-induced Lungmentioning

confidence: 99%

AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality

Luo

Alcorn

Chen

et al. 2017

The Journal of Immunology

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The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice. Interestingly, AIM2 deficiency did not affect the transcription of caspase-1 and IL-1β. In addition, AIM2-deficient mice exhibited attenuated lung injury and significantly improved survival against IAV challenges, but did not alter viral burden in the lung. However, AIM2 deficiency did not seem to affect adaptive immune response against IAV infections. Furthermore, experiments with AIM2-specific small interfering RNA–treated and AIM2-deficient human and mouse lung alveolar macrophages and type II cells indicated a macrophage-specific function of AIM2 in regulation of IAV-stimulated proinflammatory response. Collectively, our results demonstrate that influenza infection activates the AIM2 inflammasome, which plays a critical role in IAV-induced lung injury and mortality. AIM2 might serve as a therapeutic target for combating influenza-associated morbidity and mortality without compromising the host antiviral responses.

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Regulation and functions of NLRP3 inflammasome during influenza virus infection

Cited by 67 publications

References 79 publications

Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host

Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host

Viroporins and inflammasomes: A key to understand virus-induced inflammation

AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality

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