NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis DOI Creative Commons
Michiel Goris, Katiuska Passelli, Sanam Peyvandi

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(9), С. e1012527 - e1012527

Опубликована: Сен. 9, 2024

Intracellular pathogens that replicate in host myeloid cells have devised ways to inhibit the cell’s killing machinery. Pyroptosis is one of strategies used reduce pathogen replicating niche and thereby control its expansion. The intracellular Leishmania parasites can survive use neutrophils as a silent entry niche, favoring subsequent parasite dissemination into host. Here, we show mexicana induces NLRP1- caspase-1-dependent Gasdermin D (GSDMD)-mediated pyroptosis neutrophils, process critical parasite-induced pathology. In absence GSDMD, observe an increased number infected dermal two days post-infection. Using adoptive neutrophil transfer neutropenic mice, contributes regulation early after infection. role positive influence on disease outcome was further demonstrated following infection mice with neutrophil-specific deletion GSDMD. Thus, our study establishes regulator leishmaniasis

Язык: Английский

Gasdermin E dictates inflammatory responses by controlling the mode of neutrophil death DOI Creative Commons
Fengxia Ma, Laxman Ghimire, Qian Ren

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 9, 2024

Abstract Both lytic and apoptotic cell death remove senescent damaged cells in living organisms. However, they elicit contrasting pro- anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of remains incompletely understood. Here we identify Gasdermin E (GSDME) as a master switch for neutrophil pyroptotic death. tightly regulated GSDME cleavage activation aging neutrophils are mediated by proteinase-3 caspase-3, leading to pyroptosis. deficiency does not alter overall survival rate; instead, it specifically precludes pyroptosis skews towards apoptosis, thereby attenuating inflammatory responses due augmented efferocytosis macrophages. In clinically relevant acid-aspiration-induced lung injury model, neutrophil-specific deletion reduces pulmonary inflammation, facilitates inflammation resolution, alleviates injury. Thus, controlling mode death, dictates host outcomes, providing potential therapeutic target infectious diseases.

Язык: Английский

Процитировано

20
NLRP3 selectively drives IL-1β secretion by Pseudomonas aeruginosa infected neutrophils and regulates corneal disease severity DOI Creative Commons
Martin Minns,

Karl Liboro,

Tatiane S. Lima

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 20, 2023

Abstract Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β and pyroptosis. Here we examine inflammasome signaling neutrophils Pseudomonas aeruginosa strain PAO1 that expresses T3SS effectors ExoS ExoT. by requires needle translocon proteins GSDMD. In macrophages, mutants lacking ExoT ( ΔexoST ) require for secretion. While release from is also NLRC4-dependent, infection instead NLRP3-dependent driven ADP ribosyl transferase activity of ExoS. Genetic pharmacologic approaches using MCC950 reveal NLRP3 essential bacterial killing disease severity a murine model P. corneal (keratitis). Overall, these findings function ADPRT regulating subtype usage versus macrophages an unexpected role keratitis.

Язык: Английский

Процитировано

32
Therapeutic potential of quercitrin in intervertebral disc degeneration: Targeting pyroptosis and inflammation DOI Creative Commons
Xinyu Wu, Qing Pan, Chao Yao

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 156, С. 114680 - 114680

Опубликована: Апрель 22, 2025

Язык: Английский

Процитировано

1
Immunity to pathogenic fungi in the eye DOI Open Access
Serena Abbondante, Sixto M. Leal, Heather Clark

и другие.

Seminars in Immunology, Год журнала: 2023, Номер 67, С. 101753 - 101753

Опубликована: Апрель 13, 2023

Язык: Английский

Процитировано

16
Inflammasome and pyroptosis in autoimmune liver diseases DOI Creative Commons
Jixuan Wang,

Zhiwen Sun,

Jingri Xie

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 8, 2023

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), sclerosing (PSC), and IgG4-related (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which all defined by an aberrant immune system attack on liver. Most previous studies have shown that apoptosis necrosis two major modes hepatocyte death in AILDs. Recent reported inflammasome-mediated pyroptosis is critical for inflammatory response severity injury This review summarizes our present understanding inflammasome activation function, as well connections among inflammasomes, pyroptosis, AILDs, thus highlighting shared features across disease models gaps knowledge. In addition, we summarize correlation NLRP3 liver-gut axis, injury, intestinal barrier disruption PBC PSC. We differences microbial metabolic characteristics between PSC IgG4-SC, highlight uniqueness IgG4-SC. explore different roles acute chronic cholestatic complex controversial crosstalk various types cell also discuss most up-to-date developments inflammasome- pyroptosis-targeted medicines disorders.

Язык: Английский

Процитировано

15
Non-apoptotic cell death programs in cervical cancer with an emphasis on ferroptosis DOI
Mohammad Samare‐Najaf, Ali Samareh, Amir Savardashtaki

и другие.

Critical Reviews in Oncology/Hematology, Год журнала: 2023, Номер 194, С. 104249 - 104249

Опубликована: Дек. 23, 2023

Язык: Английский

Процитировано

13
Identification and Validation of Hub Genes Related to Neutrophil Extracellular Traps-Mediated Cell Damage During Myocardial Infarction DOI Creative Commons

Da Ke,

Jian Ni, Yuan Yuan

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 617 - 637

Опубликована: Фев. 1, 2024

Purpose: Studies have shown that neutrophil-mediated formation of neutrophil extracellular traps (NETs) leads to increased inflammatory response and cellular tissue damage during myocardial infarction (MI). We aimed identify validate possible hub genes in the process NETs-mediated cell damage. Methods: performed an immune infiltration analysis MI transcriptome dataset based on CIBERSORT ssGSEA algorithms. Gene expression profiles NETs (GSE178883) were used analyze physiological processes peripheral blood neutrophils after phorbol myristate acetate (PMA) stimulation. Bioinformatics machine learning algorithms utilized find candidate NETs-related datasets (GSE66360 GSE179828). generated receiver operating curve (ROC) evaluate diagnostic value genes. Next, correlation between cells was analyzed using CIBERSORT, xCell Finally, we quantitative real-time PCR (qRT-PCR) immunohistochemistry verify gene expression. Results: Immune revealed such as highly expressed patients with MI. Functional differentially (DEGs) GSE178883 indicated potential pathogenesis lies terms. Using weighted co-expression network (WGCNA) algorithms, finally identified seven (FCAR, IL1B, MMP9, NFIL3, CXCL2, ICAM1, ZFP36). The qRT-PCR results showed IL-1B, NFIL3 mRNA up-regulated group compared control. Immunohistochemical high infarcted area non-infarcted sham-operated groups. Conclusion: associated Our may provide insights into mechanisms injury Keywords: infarction, neutrophils, damage, traps, bioinformatics, endothelial

Язык: Английский

Процитировано

5
The role of inflammasome in chronic viral hepatitis DOI Creative Commons
Pin Wan, Ge Yang, Qi Cheng

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Май 16, 2024

Infections of hepatotropic viruses cause a wide array liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis hepatocellular carcinoma (HCC). Among five classical viruses, B virus (HBV) C (HCV) usually infect human persistently leading to major troubles humanity. Previous studies have revealed that several types inflammasomes are involved in infections HBV HCV. Here, we summarize current knowledge about their roles C. NLRP3 inflammasome can be activated regulated by It is found exert antiviral function or mediates inflammatory response viral depending on different experimental models. Besides inflammasome, IFI16 AIM2 participate pathological process B, NALP3 may sense HCV infection hepatocytes. The affect through its downstream secretion cytokines interleukin-1β (IL-1β) IL-18 induction pyroptosis resulting from cleaved gasdermin D (GSDMD). However, stages remains mainly unclear. More proper models should for specific future, so understand more complexity regulation multifunction effectors during infections.

Язык: Английский

Процитировано

4
Pyroptosis: A major trigger of excessive immune response in the gingiva DOI
Xueyu Xiang, Jing Zhang, Yuan Yue

и другие.

Oral Diseases, Год журнала: 2024, Номер 30(7), С. 4152 - 4160

Опубликована: Июнь 9, 2024

The gingival mucosal barrier, an important oral cavity plays a significant role in preventing pathogenic microorganism invasion and maintaining periodontal tissue health. Pathogenic of the mucosa produces large number cytokines. Among them, pyroptosis is player exacerbating immune-inflammatory responses, leading to destruction. However, mechanism immune response it triggers have not been fully elucidated. We provide overview recent advances understanding physical barrier inflammation-induced hyperimmunity.

Язык: Английский

Процитировано

3
Revisiting the potential of regulated cell death in glioma treatment: a focus on autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis, immunogenic cell death, and the crosstalk between them DOI Creative Commons

Maowen Luo,

Xingzhao Luan,

Chaoge Yang

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Авг. 9, 2024

Gliomas are primary tumors that originate in the central nervous system. The conventional treatment options for gliomas typically encompass surgical resection and temozolomide (TMZ) chemotherapy. However, despite aggressive interventions, median survival glioma patients is merely about 14.6 months. Consequently, there an urgent necessity to explore innovative therapeutic strategies treating glioma. foundational study of regulated cell death (RCD) can be traced back Karl Vogt's seminal observations cellular demise toads, which were documented 1842. In past decade, Nomenclature Committee on Cell Death (NCCD) has systematically classified delineated various forms mechanisms death, synthesizing morphological, biochemical, functional characteristics. primarily manifests two forms: accidental (ACD), caused by external factors such as physical, chemical, or mechanical disruptions; RCD, a gene-directed intrinsic process coordinates orderly response both physiological pathological cues. Advancements our understanding RCD have shed light manipulation modulation - either through induction suppression potentially groundbreaking approach oncology, holding significant promise. obstacles persist at interface research clinical application, with impediments encountered translating modalities. It increasingly apparent integrative examination molecular underpinnings imperative advancing field, particularly within framework inter-pathway synergy. this review, we provide overview including autophagy-dependent anoikis, ferroptosis, cuproptosis, pyroptosis immunogenic death. We summarize latest advancements regulate interconnections between different processes. By comprehending these connections developing targeted strategies, potential enhance therapy RCD.

Язык: Английский

Процитировано

3