Article
Multidisciplinary Sciences
Zi Chen, Linyang Ge, Shuanglan Xu, Qin Li, Linfu Zhou
Summary: This study aimed to identify a prognostic signature of pyroptosis-related genes (PRGs) in lung adenocarcinoma (LUAD) and explore the connection of PRGs with the tumor microenvironment. Through analysis of gene expression and clinical information from The Cancer Genome Atlas database, LUAD patients were classified into three subtypes and a prognostic model consisting of four PRGs was constructed. Significant correlations were observed between these prognostic PRGs and immune cell infiltration or the tumor mutational burden. Predictive nomogram results showed that BAK1 could be an independent prognostic biomarker in LUAD. Additionally, the expression level of BAK1 was validated in two independent Gene Expression Omnibus cohorts. Our findings provide insight for future studies targeting pyroptosis and the tumor microenvironment in LUAD.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Eva Hasel de Carvalho, Shivani S. Dharmadhikari, Kateryna Shkarina, Jingwei Rachel Xiong, Bruno Reversade, Petr Broz, Maria Leptin
Summary: The researchers constructed a light-responsive form of the inflammasome adaptor protein, allowing tight control of inflammasome formation within cells. By introducing this construct into zebrafish, they were able to induce inflammasome formation in individual skin cells. They found that the resulting cell death from inflammasome formation varied morphologically in different cell types.
Article
Nanoscience & Nanotechnology
Binlong Chen, Yue Yan, Ye Yang, Guang Cao, Xiao Wang, Yaoqi Wang, Fangjie Wan, Qingqing Yin, Zenghui Wang, Yunfei Li, Letong Wang, Bo Xu, Fuping You, Qiang Zhang, Yiguang Wang
Summary: The authors in this paper engineer a library of ultra-pH-sensitive nanophotosensitizers that can target specific endocytic organelles and induce pyroptotic cancer cell death in a controlled manner. By spatiotemporally targeting distinct stages of endosomal maturation, they achieve tunable cellular pyroptosis. The nanotuner platform demonstrates enhanced antitumor efficacy and minimized systemic side effects in various gasdermin-E-positive human cancers.
NATURE NANOTECHNOLOGY
(2022)
Article
Cell Biology
Snigdha Tiash, Jonathan Robert Brestoff, Clair Crewe
Summary: This article briefly reviews the current research status of mitochondria transfer and discusses a methodological framework for studying the process.
NATURE CELL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Bruna Sabatke, Izadora Volpato Rossi, Abel Sana, Leticia Bassani Bonato, Marcel I. Ramirez
Summary: The study of host-pathogen interactions has significantly increased in recent decades, with extracellular vesicles (EVs) playing an important role in facilitating intercellular communication during the interaction. This review focuses on the dynamic roles of EV release and capture during host-pathogen interactions, critically analyzing methodologies for obtaining and analyzing EVs. The review emphasizes key points to consider in EV biogenesis and uptake studies.
MOLECULAR MICROBIOLOGY
(2023)
Article
Microbiology
Varnesh Tiku, Chun Kew, Eric M. Kofoed, Yutian Peng, Ivan Dikic, Man-Wah Tan
Summary: This study reveals that A. baumannii secretes an inflammatory bioactive lipid that activates multiple pro-inflammatory signaling pathways and induces cell death. This finding contributes to a better understanding of the immune mechanisms involved in A. baumannii infection.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joelle A. J. Housmans, Guiqin Wu, Joost Schymkowitz, Frederic Rousseau
Summary: Disruptions or instabilities in protein folding can lead to the accumulation of misfolded proteins and the formation of protein aggregates, which are associated with human diseases and pose challenges in biopharmaceutical manufacturing. However, protein aggregates can also be functional and have applications in biomaterials, therapeutics, and food improvement. Understanding the steps involved in protein aggregation is crucial for developing diagnostic methods, treatments, and applications in various fields. The study of protein aggregation is challenging due to its complex and dynamic nature.
Review
Medicine, Research & Experimental
Sheng-Kai Hsu, Chia-Yang Li, I-Ling Lin, Wun-Jyun Syue, Yih-Fung Chen, Kai-Chun Cheng, Yen-Ni Teng, Yi-Hsiung Lin, Chia-Hung Yen, Chien-Chih Chiu
Summary: New types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have emerged in recent years, playing significant roles in cancer progression modulation and being closely related to immune regulation in the tumor microenvironment. Pyroptosis, in particular, has been identified as crucial for host defense and bridging innate and adaptive immunity, showing benefits for cancer immunotherapies.
Article
Microbiology
Xuqiu Lei, Yongzhi Chen, Egil Lien, Katherine A. Fitzgerald
Summary: Influenza A virus (IAV) induces multiple types of cell death, including necroptosis, apoptosis, and pyroptosis. MLKL promotes inflammasome activation and IL-1 beta processing in IAV-infected macrophages, while caspase-8 coordinates the maturation and secretion of IL-1 beta in the absence of the MLKL-inflammasome axis. MLKL and caspase-8 serve as redundant mechanisms for inflammatory cell death in response to IAV infection.
Article
Multidisciplinary Sciences
Stefan Bauernfried, Matthias J. Scherr, Andreas Pichlmair, Karl E. Duderstadt, Veit Hornung
Summary: Inflammasomes play a crucial role as intracellular sensors in pathogen infection and cellular perturbation. Human NLRP1 has been identified as a direct sensor for dsRNA, triggering activation during RNA virus infection. The NLRP1 complex binds dsRNA through its leucine-rich repeat domain, leading to activation through adenosine triphosphatase activity in its NACHT domain.
Article
Multidisciplinary Sciences
Poulomi Banerjee, Arpan R. Mehta, Raja S. Nirujogi, James Cooper, Owen G. James, Jyoti Nanda, James Longden, Karen Burr, Karina McDade, Andrea Salzinger, Evdokia Paza, Judith Newton, David Story, Suvankar Pal, Colin Smith, Dario R. Alessi, Bhuvaneish T. Selvaraj, Josef Priller, Siddharthan Chandran
Summary: Using hiPSC-MG, researchers found that reduced C9ORF72 protein is associated with impaired phagocytosis and an exaggerated immune response. Their findings also revealed dysregulation in myeloid cells as a contributor to neurodegeneration in ALS/FTD, and pharmacological activation of autophagy can ameliorate cell-autonomous functional deficits and motor neuron death in coculture.
Review
Materials Science, Multidisciplinary
Jiulong Li, Xingfa Gao, Yuguang Wang, Tian Xia, Yuliang Zhao, Huan Meng
Summary: This review systematically investigates the molecular mechanisms of immune responses induced by engineered nanomaterials (ENMs) and emphasizes the critical role of material properties in immune modulation. It also proposes the utilization of nanotechnology to develop safe and effective immunomodulation strategies, as well as discusses the challenges and opportunities for clinical translation.
Article
Cell Biology
Takayuki Uematsu, Kohsuke Tsuchiya, Noritada Kobayashi, Motoharu Seiki, Jun-ichiro Inoue, Shuichi Kaneko, Takeharu Sakamoto
Summary: The absence of Mint3 can increase resistance to Listeria monocytogenes infection and promote pyroptosis in host macrophages. Mint3 depletion affects inflammasome assembly, glycolysis, and reactive oxygen species production, influencing cell death mechanisms.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Wentao Fan, Chenchen Ding, Shuhui Liu, Xiaona Gao, Xiaofei Shen, Marthe De Boevre, Zhangshan Gao, Mengcong Li, Shuo Zhang, Yufan Miao, Wenxian Guan, Guangliang Liu, Liping Yan, Sarah De Saeger, Suquan Song
Summary: ER8 and NLRP6 are highly expressed in intestinal tissues and inhibit colitis by directly activating the NLRP6 gene expression and promoting autophagy to regulate the inflammatory response. This study reveals the importance of the ER8-NLRP6-autophagy pathway in maintaining intestinal epithelial cell homeostasis and facilitating tissue repair in colitis.
Article
Oncology
Li Liu, Wenzheng Chen, Yebei Li, Pengcheng Fu, Yi Cao, Zhengrong Li, Jianbo Xiong, Zhigang Jie
Summary: This study found that pyroptosis-related lncRNAs are differentially expressed in colorectal cancer and are associated with patient prognosis and immune characteristics.
JOURNAL OF ONCOLOGY
(2022)
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)
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)
Article
Multidisciplinary Sciences
Camila Marques-da-Silva, Barun Poudel, Rodrigo P. Baptista, Kristen Peissig, Lisa S. Hancox, Justine C. Shiau, Lecia L. Pewe, Melanie J. Shears, Thirumala-Devi Kanneganti, Photini Sinnis, Dennis E. Kyle, Prajwal Gurung, John T. Harty, Samarchith P. Kurup
Summary: Malaria, caused by Plasmodium parasites, is a severe disease affecting millions of people worldwide. The researchers have discovered a pathway of natural immunity critical for the control of malaria in the liver, which involves the sensing of Plasmodium DNA by cytosolic AIM2 receptors in infected hepatocytes, leading to Caspase-1 activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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)
Editorial Material
Immunology
R. K. Subbarao Malireddi, Thirumala-Devi Kanneganti
Summary: NLRP3 inflammasome regulation is crucial for controlling cell death and inflammation. Recent research suggests that, while a two-step model involving NEK7 is observed in murine cells, humans exhibit transcription-independent NLRP3 activation by bypassing NEK7 through IKK beta.
TRENDS IN IMMUNOLOGY
(2022)
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.
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)
Editorial Material
Biochemistry & Molecular Biology
Rebecca E. Tweedell, Sivakumar Prasanth Kumar, Thirumala-Devi Kanneganti
Summary: The past two decades of research have revealed new innate immune sensing and cell death pathways that are relevant to diseases. Further molecular characterization of these pathways and understanding their crosstalk and functional redundancies will contribute to the development of therapeutic strategies.
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.
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.
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
