Author Response: Caspase-1 activates gasdermin A in non-mammals DOI Open Access
Zachary P. Billman,

Stephen B. Kovacs,

Bo Wei

и другие.

Опубликована: Фев. 19, 2024

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase granzyme proteases cleave linker regions of activate GSDMB, E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis gasdermin family. A gene duplication GSDMA common ancestor caecilian amphibians, reptiles birds gave rise GSDMA-D mammals. Uniquely our tree, amphibian, reptile bird group separate clade than mammal Remarkably, numerous species contain caspase-1 cleavage sites like YVAD or FASD linker. We show from birds, all cleaved by caspase-1. Thus, was originally host-encoded protease In mammals site is disrupted; instead, new protein, GSDMD, target Mammal uses exosite interactions with GSDMD C-terminal domain confer specificity this interaction, whereas stereotypical tetrapeptide sequence Our results reveal an evolutionarily stable association between family, albeit shifting one. Caspase-1 repeatedly changes its over time at speciation junctures, initially cleaving GSDME fish, then amphibians/reptiles/birds, finally mammals.We demonstrate engage pyroptosis using GS-DMA, filling gap which cleaves fish

Язык: Английский

Caspase-1 activates gasdermin A in non-mammals DOI Creative Commons
Zachary P. Billman,

Stephen B. Kovacs,

Bo Wei

и другие.

eLife, Год журнала: 2024, Номер 12

Опубликована: Март 18, 2024

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase granzyme proteases cleave linker regions of activate GSDMB, E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis gasdermin family. A gene duplication GSDMA common ancestor caecilian amphibians, reptiles, birds gave rise GSDMA–D mammals. Uniquely our tree, amphibian, reptile, bird group separate clade than mammal Remarkably, numerous species contain caspase-1 cleavage sites like YVAD or FASD linker. We show from birds, reptiles all cleaved by caspase-1. Thus, was originally host-encoded protease In mammals site is disrupted; instead, new protein, GSDMD, target Mammal uses exosite interactions with GSDMD C-terminal domain confer specificity this interaction, whereas stereotypical tetrapeptide sequence Our results reveal an evolutionarily stable association between family, albeit shifting one. Caspase-1 repeatedly changes its over time at speciation junctures, initially cleaving GSDME fish, then amphibians/reptiles/birds, finally

Язык: Английский

Процитировано

10
Inflammasome‐mediated pyroptosis in defense against pathogenic bacteria DOI
Changhoon Oh,

Todd J. Spears,

Youssef Aachoui

и другие.

Immunological Reviews, Год журнала: 2024, Номер unknown

Опубликована: Окт. 15, 2024

Macrophages, neutrophils, and epithelial cells are pivotal components of the host's immune response against bacterial infections. These employ inflammasomes to detect various microbial stimuli during infection, triggering an inflammatory aimed at eradicating pathogens. Among these responses, pyroptosis, a lytic form cell death, plays crucial role in eliminating replicating bacteria recruiting combat invading pathogen. The immunological function pyroptosis varies across macrophages, cells, aligning with their specific roles within innate system. This review centers on elucidating resisting gram-negative infections, particular focus mechanisms play intestinal cells. Additionally, we underscore type-specific vivo contexts defense.

Язык: Английский

Процитировано

8
HCAR2 Modulates the Crosstalk between Mammary Epithelial Cells and Macrophages to Mitigate Staphylococcus aureus Infection in the Mouse Mammary Gland DOI Creative Commons
Xin Ran, Kefei Li, Yutao Li

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Abstract Staphylococcus aureus ( S. ) is a major zoonotic pathogen, with mammary gland infections contributing to mastitis, condition that poses significant health risks lactating women and adversely affects the dairy industry. Therefore, understanding immune mechanisms underlying caused by essential for developing targeted therapeutic strategies against mastitis. This study identified hydroxycarboxylic acid receptor 2 (HCAR2) as potential regulator of infection in glands. It demonstrated HCAR2 deficiency exacerbates inflammatory response disrupts blood‐milk barrier during infection, NLRP3 inflammasome‐mediated pyroptosis playing central role. Activation HCAR2, on other hand, suppressed CMPK2 expression, thereby mitigating mitochondrial damage mouse epithelial cells (mMECs) induced . Additionally, DNA (mtDNA) released from ‐infected mMECs activates cGAS/STING signaling pathway macrophages, impairing their bactericidal activity. In conclusion, this highlights critical role provides theoretical basis identifying targets such infections.

Язык: Английский

Процитировано

1
Caspase-1 activates gasdermin A in non-mammals DOI Creative Commons
Zachary P. Billman,

Stephen B. Kovacs,

Bo Wei

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Ноя. 22, 2023

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase granzyme proteases cleave linker regions of activate GSDMB, E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis gasdermin family. A gene duplication GSDMA common ancestor caecilian amphibians, reptiles, birds gave rise GSDMA–D mammals. Uniquely our tree, amphibian, reptile, bird group separate clade than mammal Remarkably, numerous species contain caspase-1 cleavage sites like YVAD or FASD linker. We show from birds, reptiles all cleaved by caspase-1. Thus, was originally host-encoded protease In mammals site is disrupted; instead, new protein, GSDMD, target Mammal uses exosite interactions with GSDMD C-terminal domain confer specificity this interaction, whereas stereotypical tetrapeptide sequence Our results reveal an evolutionarily stable association between family, albeit shifting one. Caspase-1 repeatedly changes its over time at speciation junctures, initially cleaving GSDME fish, then amphibians/reptiles/birds, finally

Язык: Английский

Процитировано

13
Regulating pyroptosis by mesenchymal stem cells and extracellular vesicles: A promising strategy to alleviate intervertebral disc degeneration DOI Open Access
Sheng Yang, Yongbo Zhang, Qing Peng

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 116001 - 116001

Опубликована: Дек. 20, 2023

Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate heavy burden on society. IVDD characterized by decrease in nucleus pulposus cells (NPCs) endogenous mesenchymal stem (MSCs), degradation the extracellular matrix, macrophage infiltration, blood vessel nerve ingrowth. To date, therapeutic approaches regarding mainly include conservative treatment surgical intervention. However, both only relieve symptoms rather than stop or revert progression IVDD, since pathogenesis not yet clear. Pyroptosis, Caspase family dependence conducted Gasdermin family, newly discovered mode programmed cell death. Pyroptosis has been observed NPCs, annulus fibrosus (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial neurons may contribute IVDD. MSCs are kind pluripotent that be found almost all tissues. have strong ability secrete vesicles (EVs), contain exosomes, microvesicles apoptotic bodies. EVs derived from play an important role pyroptosis regulation could beneficial for alleviating This review focuses clarifying improve MSCs.

Язык: Английский

Процитировано

12
Bacterial Programmed Cell Death Induced by Nanotherapeutic Strategies DOI
Yanling Hu, Jinjun Shao, Heng Dong

и другие.

ACS Materials Letters, Год журнала: 2024, Номер 6(9), С. 4209 - 4229

Опубликована: Авг. 19, 2024

Programmed cell death (PCD) is crucial for renewal, embryogenesis, the immune response, tissue growth regulation, and other essential biological processes. Recent evidence underscores potential of harnessing PCD to combat bacterial infections, particularly in eradicating antibiotic-resistant superbugs. Extensive efforts have been devoted developing PCD-mediated anti-infective agents by drawing insights from materials science, chemistry, immunology, microbiology. In this review, challenges addressing infections PCD-based approaches revolutionize treatment are first summarized discussed. Then, a comprehensive examination nanoantibacterial therapy, encompassing various pathways, such as apoptosis, ferroptosis, cuproptosis, immunogenic death, NETosis, autophagy, pyroptosis, provided. Finally, barriers prospects PCD-driven antimicrobial strategies explored.

Язык: Английский

Процитировано

5
Pyroptosis regulation by Salmonella effectors DOI Creative Commons
Yuan Meng, Qianjin Zhang, Ming Xu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 23, 2024

The genus Salmonella contains the most common foodborne pathogens frequently isolated from food-producing animals and is responsible for zoonotic infections in humans animals. infection can cause intestinal damage, resulting inflammation disruption of homeostasis more severe cases lead to bacteremia. Pyroptosis, a proinflammatory form programmed cell death, involved many disease processes. Inflammasomes, pyroptosis, along with their respective signaling cascades, are instrumental preservation homeostasis. In recent years, in-depth study our comprehension virulence factors effector proteins has reached an extensive level, deficit persists knowledge regarding intrinsic pathogenic mechanisms about necessitating continued pursuit understanding investigation. this review, we discuss occurrence pyroptosis induced by effectors provide new ideas elucidating regulatory through which trigger could pave way novel concepts strategies clinical prevention treatment associated diseases.

Язык: Английский

Процитировано

4
Unanticipated Loss of Inflammasomes in Birds DOI Creative Commons
Zachary P. Billman, Dustin C. Hancks,

Edward A Miao

и другие.

Genome Biology and Evolution, Год журнала: 2024, Номер 16(7)

Опубликована: Июль 1, 2024

Abstract Inflammasomes are multiprotein complexes that form in response to ligands originating from pathogens as well alterations of normal cell physiology caused by infection or tissue damage. These structures engage a robust inflammatory immune eradicates environmental microbes before they cause disease, and slow the growth bona fide pathogens. Despite their undeniable utility immunity, inflammasomes radically reduced birds. Perhaps most surprising is that, within all birds, NLRP3 retained, while its signaling adapter ASC lost, suggesting signals via novel unknown adapter. Crocodilian reptiles turtles, which share more recent common ancestor with retain many lost inflammasome components, indicating deletion occurred after birds diverged crocodiles. Some bird lineages have even extensive loss, songbirds continuing pare down until only CARD8 remain. Remarkably, caspase-1 but downstream targets caspase-1: IL-1β, IL-18, YVAD-linker encoding gasdermin A. This suggests can signal through alternative proteases activate cytokine maturation pyroptosis songbirds. observations may reveal new contexts activation be relevant mammalian suggest avenues research uncover enigmatic nature poorly understood inflammasome.

Язык: Английский

Процитировано

3
An Update on the Study of the Molecular Mechanisms Involved in Autophagy during Bacterial Pathogenesis DOI Creative Commons
Md. Ataur Rahman,

Amily Sarker,

Mohammed Ayaz

и другие.

Biomedicines, Год журнала: 2024, Номер 12(8), С. 1757 - 1757

Опубликована: Авг. 5, 2024

Autophagy is a unique catabolic process that degrades irrelevant or damaged components in eukaryotic cells to maintain homeostasis and eliminate infections from pathogenesis. Pathogenic bacteria have developed many autophagy manipulation techniques affect host immune responses intracellular bacterial pathogens evolved avoid xenophagy. However, reducing its effectiveness as an innate response has not yet been elucidated. Bacterial cause infected cell-autonomous defense mechanism the pathogen. harmful learned control defeat defenses. Intracellular can stimulate autophagy, while others inhibit it prevent xenophagy lysosomal breakdown. This review evaluates putative functions for regulating infection, emphasizing successful strategies disrupt exploit this defense, efficiency immunity. Instead, animal models show autophagy-associated proteins influence pathogenicity outside of We also examine consequences complex interaction between light current efforts modify develop host-directed therapeutics fight infections. Therefore, effective subvert xenophagy, although Finally, implies how affects therapy

Язык: Английский

Процитировано

3
Guards and decoys: RIPoptosome and inflammasome pathway regulators of bacterial effector-triggered immunity DOI Creative Commons

Haleema Sadia Malik,

James B. Bliska

PLoS Pathogens, Год журнала: 2025, Номер 21(1), С. e1012884 - e1012884

Опубликована: Янв. 30, 2025

Virulent microbes produce proteins that interact with host cell targets to promote pathogenesis. For example, virulent bacterial pathogens have called effectors are typically enzymes and secreted into cells. To detect respond the activities of effectors, diverse phyla organisms evolved effector-triggered immunity (ETI). In ETI, often sensed indirectly by detection their virulence in ETI mechanisms can be complex involve several classes proteins. Guards monitor functional or physical integrity another protein, guardee decoy, become activated initiate an immune response when decoy is modified disrupted effector. A has intrinsic anti-pathogen function intended target structurally mimics a protein activity unintentionally targeted individual domain integrated guard. Here, we review origins focus on 5 mechanisms, which key steps pathway include activation caspase RIPoptosome inflammasome, formation pores plasma membrane, release cytokines ending death pyroptosis. Survey been shown protective mouse models infection, reveal how distinct regulators inflammasome pathways act as guards decoys trigger ETI. Common themes highlighted limited mechanistic understanding bactericidal discussed.

Язык: Английский

Процитировано

0