Review
Medicine, Research & Experimental
Zehong Qi, Lili Zhu, Kangkai Wang, Nian Wang
Summary: PANoptosis is a novel form of programmed cell death characterized by the assembly of PANoptosome complex. Different PANoptosomes, defined by distinct sensors and regulators, activate pyroptosis, apoptosis, and necroptosis simultaneously through different catalytic effectors. PANoptosis is considered as a prospective therapeutic target for various diseases.
Article
Immunology
Rajendra Karki, SangJoon Lee, Raghvendra Mall, Nagakannan Pandian, Yaqiu Wang, Bhesh Raj Sharma, Subbarao R. K. Malireddi, Dong Yang, Sanja Trifkovic, Jacob A. Steele, Jon P. Connelly, Gella Vishwanath, Mitnala Sasikala, Duvvur Nageshwar Reddy, Peter Vogel, Shondra M. Pruett-Miller, Richard Webby, Colleen Beth Jonsson, Thirumala-Devi Kanneganti
Summary: A study found that during coronavirus infection, IFN induces ZBP1-mediated inflammatory cell death, limiting the efficacy of IFN therapy, inhibiting ZBP1 activity may improve the effectiveness of IFN therapy.
SCIENCE IMMUNOLOGY
(2022)
Review
Oncology
Mingxia Jiang, Ling Qi, Lisha Li, Yiming Wu, Dongfeng Song, Yanjing Li
Summary: Caspase-8 is a key player in cancer, involved in multiple programmed cell death modes and closely associated with tumor growth, invasion, therapeutic resistance, etc.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Review
Oncology
Hantao Cai, Mingming Lv, Tingting Wang
Summary: PANoptosis is a novel form of programmed cell death that combines the features of apoptosis, pyroptosis, and necroptosis. Historically, these cell death processes were considered independent, but evidence suggests that they exhibit cross talk and interactions, leading to the development of PANoptosis concept.
Review
Biochemistry & Molecular Biology
Yaqiu Wang, Thirumala-Devi Kanneganti
Summary: Pyroptosis, apoptosis and necroptosis are well-defined programmed cell death pathways, with growing evidence showing extensive crosstalk among them. PANoptosis, regulated by the PANoptosome complex, combines features of pyroptosis, apoptosis, and/or necroptosis. This new concept is critically involved in various diseases and may inform the development of new therapeutics.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Immunology
SuHyeon Oh, SangJoon Lee
Summary: Innate immunity is a crucial defense against pathogens, including viruses, and ZBP1 plays a central role in regulating inflammatory cell death during viral infection. By sensing viral RNA, ZBP1 induces PANoptosis to protect host cells, but some viruses, like coronaviruses, can exploit this process to cause harm to the host. Understanding the molecular mechanism of ZBP1-derived PANoptosis is important for improving therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Jessica M. Gullett, Rebecca E. Tweedell, Thirumala-Devi Kanneganti
Summary: The article discusses the cell death pathways and their interactions in the innate immune system. By viewing them through the lens of an integrated inflammatory cell death concept called PANoptosis, the diverse descriptions of interactions can be better understood. The article also introduces PANoptosomes as multifaceted macromolecular complexes regulating PANoptosis, and highlights the importance of PANoptosis in infections, diseases, and cancers. Having a holistic understanding of cell death is crucial for identifying new therapeutic strategies.
Review
Immunology
Ling Qi, Li Wang, Mengru Jin, Mingxia Jiang, Lisha Li, Yanjing Li
Summary: Caspase-6, a member of the caspase family, plays a vital role in mediating cell death. Recent studies have shown that it mediates PANoptosis and is involved in tumorigenesis and anti-tumor immunity. Understanding the function of caspase-6 in PANoptosis is important for cancer prevention and treatment.
Article
Immunology
Suhyeon Oh, Jihye Lee, Jueun Oh, Gyoengju Yu, Haesun Ryu, Daesik Kim, Sangjoon Lee
Summary: Inflammasomes are important for innate immune defense and can sense and defend against pathogens. This study discovered that multiple inflammasome sensors can be simultaneously activated by multiple ligands, leading to various types of inflammatory cell death. Additionally, NLRP3, AIM2, NLRC4, and Pyrin were found to be members of a large multiprotein complex that drives PANoptosis.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Diego A. Rodriguez, Giovanni Quarato, Swantje Liedmann, Bart Tummers, Ting Zhang, Cliff Guy, Jeremy Chase Crawford, Gustavo Palacios, Stephane Pelletier, Halime Kalkavan, Jeremy J. P. Shaw, Patrick Fitzgerald, Mark J. Chen, Siddharth Balachandran, Douglas R. Green
Summary: This study identifies a molecular mechanism whereby Caspase-8 and FADD suppress spontaneous necroptotic cell death. The absence of Caspase-8 or FADD leads to the activation of RIPK3 and MLKL, resulting in necroptosis. This process relies on the nucleic acid sensor ZBP1 and its associated signaling pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Wen Chen, Jessica M. M. Gullett, Rebecca E. E. Tweedell, Thirumala-Devi Kanneganti
Summary: Regulated cell death (RCD) is important for host survival during pathogen invasion and cellular disturbances. This review focuses on the newly discovered RCD pathway called PANoptosis, which is an inflammatory cell death pathway regulated by PANoptosome complexes. The article discusses the molecular components of PANoptosomes, their assembly, activation, regulation, and their link to diseases.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Hayley Muendlein, Wilson M. Connolly, Zoie Magri, Irina Smirnova, Vladimir Ilyukha, Avishekh Gautam, Alexei Degterev, Alexander Poltorak
Summary: In this study, the TRIF-dependent complex plays a crucial role in cell death and inflammation response, particularly in the context of bacterial infection. The constitutive binding between ZBP1 and RIPK1 is essential for TRIFosome interactions, caspase-8-mediated cell death, and inflammasome activation. This research provides an alternative model of pro-death complex formation reliant on TRIF signaling, demonstrating a non-canonical cell death pathway controlled by a complex of FADD, RIPK1, caspase-8, and ZBP1.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Lam Nhat Nguyen, Thirumala-Devi Kanneganti
Summary: Viral infections can activate programmed cell death (PCD) pathways, including pyroptosis, apoptosis, and necroptosis. The emerging concept of PANoptosis suggests extensive crosstalk between these PCD pathways. PANoptosis plays a significant role in regulating viral infection, but it can also have different effects on host defense and viral pathogenesis.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Virology
R. K. Subbarao Malireddi, Bhesh Raj Sharma, Ratnakar R. Bynigeri, Yaqiu Wang, Jianlin Lu, Thirumala-Devi Kanneganti
Summary: This study investigates the role of MLKL in regulating IAV-induced cell death and NLRP3 inflammasome activation. The results indicate that IAV induces inflammatory cell death through the ZBP1-PANoptosome, partially dependent on RIPK3 at later timepoints and independent of MLKL throughout all timepoints. Additionally, NLRP3 inflammasome activation is unaffected in MLKL-deficient cells, suggesting that MLKL and MLKL-dependent necroptosis do not act upstream of NLRP3 inflammasome activation, IL-1 beta maturation, and lytic cell death during IAV infection.
Review
Dentistry, Oral Surgery & Medicine
Aopeng Zhang, Chenchen Zhang, Yuhan Zhang, Tao Hu, Ran Cheng
Summary: This systematic review aims to verify the presence of PANoptosis in periodontitis based on published literature on cell death in periodontitis. The review analyzed in vitro cellular experiments, in vivo rodent studies, and clinical studies from major databases. The findings indicate that pyroptosis, necroptosis, and apoptosis can be induced by periodontal pathogens in different cell types. Three modes of cell death were detected in rodent periodontitis models, and clinical studies showed elevated levels of key proteins related to cell death in periodontitis. The results reveal complex interactions between different cell death pathways and the potential for PANoptosis in periodontitis.
Review
Medical Laboratory Technology
Bhesh Raj Sharma, Thirumala-Devi Kanneganti
Summary: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, with inflammation being a key risk factor. Inflammasomes, multiprotein immune complexes, play a crucial role in maintaining gut homeostasis and regulating inflammation. They have been shown to be involved in colitis and colitis-associated CRC, through the release of interleukin-1 beta and IL-18. Different inflammasome sensors provide protection against colitis-associated CRC through both effector cytokine-dependent and -independent mechanisms. Inflammasomes also contribute to PANoptosomes and PANoptosis, which are forms of innate immune inflammatory cell death. Understanding the mechanisms and functions of inflammasomes in CRC could lead to potential therapeutic targets.
TRANSLATIONAL RESEARCH
(2023)
Review
Immunology
Rajendra Karki, Thirumala-Devi Kanneganti
Summary: ADAR1 and ZBP1 are two mammalian proteins with Z alpha domains that bind to nucleic acids. They play crucial roles in regulating various biological processes. Recent studies have expanded our understanding of their functions, establishing their fundamental regulation of innate immune responses. This review discusses their roles in innate immune responses in development and disease.
TRENDS IN IMMUNOLOGY
(2023)
Article
Microbiology
Shishir Singh, Mateo Murillo-Leon, Niklas Sebastian Endres, Ailan Farid Arenas Soto, Jorge Enrique Gomez-Marin, Florence Melbert, Thirumala-Devi Kanneganti, Masahiro Yamamoto, Claudia Campos, Jonathan Charles Howard, Gregory Alan Taylor, Tobias Steinfeldt
Summary: Toxoplasmosis is a common parasitic zoonosis caused by Toxoplasma gondii, which infects virtually all warm-blooded animals including humans. This study identifies a virulence effector, ROP39, in T. gondii that specifically targets Irgb10 to evade IRG-mediated control, increasing its pathogenicity. This finding contributes to our understanding of the coevolutionary relationship between T. gondii and mice, which are important for transmission.
Article
Multidisciplinary Sciences
Joo-Hui Han, Rebecca E. Tweedell, Thirumala-Devi Kanneganti
Summary: Innate immunity is the first line of defense against pathogens and sterile insults. Understanding the activation and regulation of innate immune programmed cell death (PCD) is crucial for characterizing immune responses and identifying therapeutic targets across diseases.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Multidisciplinary Sciences
Lalita Mazgaeen, Matthew Yorek, Saurabh Saini, Peter Vogel, David K. Meyerholz, Thirumala-Devi Kanneganti, Prajwal Gurung
Summary: Mice with a specific amino acid substitution in SHP1 protein (Ptpn6(spin) mice) develop an autoinflammatory disease. When Ptpn6(spin) bone marrow cells are transferred into Cd47-deficient mice, marked weight loss and death occur. The study suggests that gut leakage caused by pathogenic neutrophils may contribute to the morbidity and mortality in Cd47(-/-) mice receiving Ptpn6(spin) cells. IL-1 blockade with anakinra can rescue the disease phenotype.
Article
Biochemistry & Molecular Biology
Balamurugan Sundaram, Nagakannan Pandian, Raghvendra Mall, Yaqiu Wang, Roman Sarkar, Hee Jin Kim, R. K. Subbarao Malireddi, Rajendra Karki, Laura J. Janke, Peter Vogel, Thirumala-Devi Kanneganti
Summary: Cytosolic innate immune sensors, such as NLRP12, play a critical role in host defense and can induce inflammatory cell death. This study found that NLRP12 is activated by heme plus PAMPs or TNF, leading to inflammasome and PANoptosome activation, cell death, and inflammation. By understanding this pathway, it is possible to identify potential drug targets for hemolytic and inflammatory diseases.
Review
Immunology
Wen Chen, Jessica M. M. Gullett, Rebecca E. E. Tweedell, Thirumala-Devi Kanneganti
Summary: Regulated cell death (RCD) is important for host survival during pathogen invasion and cellular disturbances. This review focuses on the newly discovered RCD pathway called PANoptosis, which is an inflammatory cell death pathway regulated by PANoptosome complexes. The article discusses the molecular components of PANoptosomes, their assembly, activation, regulation, and their link to diseases.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
R. K. Subbarao Malireddi, Ratnakar R. Bynigeri, Raghvendra Mall, Eswar Kumar Nadendla, Jon P. Connelly, Shondra M. Pruett-Miller, Thirumala-Devi Kanneganti
Summary: Transforming growth factor-beta-activated kinase 1 (TAK1) is a central regulator of innate immunity, cell death, inflammation, and cellular homeostasis. Many pathogens carry TAK1 inhibitors (TAK1i), but inhibition or deletion of TAK1 induces spontaneous inflammatory cell death, PANoptosis, which promotes pathological inflammation. Therefore, understanding the molecular mechanisms that regulate TAK1i-induced cell death is crucial.
Review
Immunology
Rajendra Karki, Thirumala-Devi Kanneganti
Summary: The innate immune response is the first line of defense against infection and disease. Regulated cell death (RCD), specifically PANoptosis, plays a crucial role in innate immune activation. Recent studies have discovered the importance of Z-DNA-binding protein 1 (ZBP1) as an activator of PANoptosis, which is regulated by the PANoptosome, during influenza A virus infection and other infections.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Editorial Material
Oncology
Rebecca E. Tweedell, Thirumala-Devi Kanneganti
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biology
R. K. Subbarao Malireddi, Ratnakar R. Bynigeri, Raghvendra Mall, Jon P. Connelly, Shondra M. Pruett-Miller, Thirumala-Devi Kanneganti
Summary: This study utilized a genome-wide screening approach to identify host factors and cellular death mechanisms associated with beta-coronavirus infection. The findings revealed key factors involved in innate immune processes and provided new targets for therapeutic development against beta-coronavirus infections.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Wen Chen, Thirumala-Devi Kanneganti
Article
Immunology
Suhyeon Oh, Jihye Lee, Jueun Oh, Gyoengju Yu, Haesun Ryu, Daesik Kim, Sangjoon Lee
Summary: Inflammasomes are important for innate immune defense and can sense and defend against pathogens. This study discovered that multiple inflammasome sensors can be simultaneously activated by multiple ligands, leading to various types of inflammatory cell death. Additionally, NLRP3, AIM2, NLRC4, and Pyrin were found to be members of a large multiprotein complex that drives PANoptosis.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)