PANoptosis: A Unique Innate Immune Inflammatory Cell Death Modality

Nagakannan, Pandian; Kanneganti, Thirumala‐Devi

doi:10.4049/jimmunol.2200508

Cited by 72 publications

(59 citation statements)

References 133 publications

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“…These findings suggest that SARS-CoV-2 infection induces PANoptosis, a unique innate immune inflammatory cell death pathway regulated by PANoptosomes, complexes that integrate molecules from other cell death pathways. The totality of biological effects in PANoptosis cannot be individually accounted for by pyroptosis, apoptosis, or necroptosis alone [ 12 , 13 , 108 – 114 , 115 , 116 ]. To date, two prototypical PANoptosomes have been biochemically identified: the Z-DNA binding domain protein 1 (ZBP1)-PANoptosome [ 113 , 117 ], and the AIM2-PANoptosome [ 118 ].…”

Section: Cell Death In Covid-19 Pathogenesismentioning

confidence: 99%

“…IFNs not only induce the expression of ISGs to block viral replication, but they also upregulate cell death mediators such as ZBP1 (Fig. 2), an innate immune sensor known to activate PANoptosis [13,[114][115][116][117][118]149]. The administration of type I IFN promotes lethality associated with inflammation and PANoptosis in the lungs of mice infected with MHV, while this is prevented in Zbp1 -/mice [13].…”

Section: Ifn Signaling In Covid-19 Pathogenesismentioning

confidence: 99%

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Innate immunity, cytokine storm, and inflammatory cell death in COVID-19

Karki

Kanneganti

2022

J Transl Med

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The innate immune system serves as the first line of defense against invading pathogens; however, dysregulated innate immune responses can induce aberrant inflammation that is detrimental to the host. Therefore, careful innate immune regulation is critical during infections. The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in global morbidity and mortality as well as socio-economic stresses. Innate immune sensing of SARS-CoV-2 by multiple host cell pattern recognition receptors leads to the production of various pro-inflammatory cytokines and the induction of inflammatory cell death. These processes can contribute to cytokine storm, tissue damage, and acute respiratory distress syndrome. Here, we discuss the sensing of SARS-CoV-2 to induce innate immune activation and the contribution of this innate immune signaling in the development and severity of COVID-19. In addition, we provide a conceptual framework for innate immunity driving cytokine storm and organ damage in patients with severe COVID-19. A better understanding of the molecular mechanisms regulated by innate immunity is needed for the development of targeted modalities that can improve patient outcomes by mitigating severe disease.

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Section: Cell Death In Covid-19 Pathogenesismentioning

confidence: 99%

Section: Ifn Signaling In Covid-19 Pathogenesismentioning

confidence: 99%

Innate immunity, cytokine storm, and inflammatory cell death in COVID-19

Karki

Kanneganti

2022

J Transl Med

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“…When RIPK3 is phosphorylated, oligomerization of MLKL is initiated and subsequently inserts into the plasma membrane of the cell, leading to pore formation and cell rupture ( Tummers and Green, 2017 ). Caspase-8 is involved in apoptosis and pyroptosis mechanisms of cell death, and when caspase-8 is inhibited RIPK1 interacts with RIPK3 leading to necroptosis ( Pandian and Kanneganti, 2022 ). Pyroptosis is another type of inflammatory programmed cell death triggered by inflammasome activation, and for a long time, it was considered to be caspase-1-mediated in response to bacterial challenge.…”

Section: Discussionmentioning

confidence: 99%

Caspase-8 but not caspase-7 influences inflammasome activation to act in control of Brucella abortus infection

et al. 2022

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Programmed cell death (PCD) is an important mechanism of innate immunity against bacterial pathogens. The innate immune PCD pathway involves the molecules caspase-7 and caspase-8, among others. Brucella abortus is a gram-negative bacterium that causes a zoonotic disease termed brucellosis. The innate immune response against this pathogen involves activation of inflammasome components and induction of pyroptosis. However, no studies so far have revealed the role of caspase-7 or caspase-8 during this bacterial infection. Herein, we demonstrate that caspase-7 is dispensable for caspase-1 processing, IL-1β secretion and cell death in macrophages. Additionally, caspase-7 deficient animals control B. abortus infection as well as the wild type mice. Furthermore, we addressed the role of caspase-8 in inflammasome activation and pyroptosis during this bacterial infection. Macrophages deficient in caspase-8 secreted reduced amounts of IL-1β that parallels with diminished caspase-1 activity when compared to wild type cells. Additionally, caspase-8 KO macrophages showed reduced LDH release when compared to wild type, suggesting that caspase-8 may play an important role in pyroptosis in response to B. abortus. Finally, caspase-8 KO animals were more susceptible to Brucella infection when compared to wild type mice. Overall, this study contributes to a better understanding of the involvement of caspase-7 and caspase-8 in innate immunity against B. abortus infection.

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“…Notably, Kanneganti et al found that synergism of TNF-α and IFN-γ induced PANoptosis, and in turn, TNF-α and IFN-γ-mediated PANoptosis maintained the status of “cytokine storm”, which is extremely critical for the pathogenic processes of COVID-19 [ 133 ]. PANoptosis is activated by specific stimulus and modulated by its core “PANoptosome” complex that provides a molecular scaffold for extensive crosstalk of key molecules among pyroptosis, apoptosis, and necroptosis [ 134 ]. Whether PANoptosis is involved in the maintenance of ASFV-induced “cytokine storm” status and which cytokines synergize to drive the PANoptosis during ASFV infection deserve further investigation.…”

Section: Future Perspectivementioning

confidence: 99%

Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis

Zhu

Deng³

et al. 2023

Viruses

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African swine fever (ASF) causes high morbidity and mortality of both domestic pigs and wild boars and severely impacts the swine industry worldwide. ASF virus (ASFV), the etiologic agent of ASF epidemics, mainly infects myeloid cells in swine mononuclear phagocyte system (MPS), including blood-circulating monocytes, tissue-resident macrophages, and dendritic cells (DCs). Since their significant roles in bridging host innate and adaptive immunity, these cells provide ASFV with favorable targets to manipulate and block their antiviral activities, leading to immune escape and immunosuppression. To date, vaccines are still being regarded as the most promising measure to prevent and control ASF outbreaks. However, ASF vaccine development is delayed and limited by existing knowledge gaps in viral immune evasion, pathogenesis, etc. Recent studies have revealed that ASFV can employ diverse strategies to interrupt the host defense mechanisms via abundant self-encoded proteins. Thus, this review mainly focuses on the antagonisms of ASFV-encoded proteins towards IFN-I production, IFN-induced antiviral response, NLRP3 inflammasome activation, and GSDMD-mediated pyroptosis. Additionally, we also make a brief discussion concerning the potential challenges in future development of ASF vaccine.

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PANoptosis: A Unique Innate Immune Inflammatory Cell Death Modality

Cited by 72 publications

References 133 publications

Innate immunity, cytokine storm, and inflammatory cell death in COVID-19

Innate immunity, cytokine storm, and inflammatory cell death in COVID-19

Caspase-8 but not caspase-7 influences inflammasome activation to act in control of Brucella abortus infection

Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis

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