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Artikel ; Online: Quantifying Cell Death Induced by the NLRC4 Inflammasome.

Emming, Stefan / Monteleone, Mercedes M / Kambara, Hiroto / Starchenko, Alina / Alley, Jennifer / Nolan, Michael A / Li, Wei / Kilty, Iain / Schroder, Kate

Methods in molecular biology (Clifton, N.J.)

2023 Band 2696, Seite(n) 199–210

Abstract: The Nod-like Receptor (NLR) apoptosis inhibitory proteins (NAIPs) are cytosolic receptors that sense cytosolic bacterial proteins. NAIP ligation induces its association with NLRC4, leading to the assembly of the NAIP/NLRC4 inflammasome, which induces the ...

Abstract	The Nod-like Receptor (NLR) apoptosis inhibitory proteins (NAIPs) are cytosolic receptors that sense cytosolic bacterial proteins. NAIP ligation induces its association with NLRC4, leading to the assembly of the NAIP/NLRC4 inflammasome, which induces the activation of the caspase-1 protease. Caspase-1 then cleaves pro-interleukin (IL)-1β, pro-IL-18, and gasdermin D and induces a form of pro-inflammatory cell death, pyroptosis. These processes culminate in host defense against bacterial infection. Here we describe methods for activating NAIP/NLRC4 inflammasome signalling in human and murine macrophages and quantifying inflammasome-induced cell death.
Mesh-Begriff(e)	Animals ; Mice ; Humans ; Inflammasomes/metabolism ; Calcium-Binding Proteins/metabolism ; Apoptosis Regulatory Proteins/metabolism ; Cell Death ; Caspases/metabolism ; Caspase 1/metabolism ; CARD Signaling Adaptor Proteins/metabolism
Chemische Substanzen	Inflammasomes ; Calcium-Binding Proteins ; Apoptosis Regulatory Proteins ; Caspases (EC 3.4.22.-) ; Caspase 1 (EC 3.4.22.36) ; NLRC4 protein, human ; CARD Signaling Adaptor Proteins
Sprache	Englisch
Erscheinungsdatum	2023-08-14
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3350-2_13
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Palmitoylation of gasdermin D directs its membrane translocation and pore formation in pyroptosis.

Balasubramanian, Arumugam / Ghimire, Laxman / Hsu, Alan Y / Kambara, Hiroto / Liu, Xing / Hasegawa, Tomoya / Xu, Rong / Tahir, Muhammad / Yu, Hongbo / Lieberman, Judy / Luo, Hongbo R

bioRxiv : the preprint server for biology

2023

Abstract: Gasdermin D (GSDMD)-mediated macrophage pyroptosis plays a critical role in inflammation and host defense. Plasma membrane perforation elicited by caspase-cleaved GSDMD N-terminal domain (GSDMD-NT) triggers membrane rupture and subsequent pyroptotic cell ...

Abstract	Gasdermin D (GSDMD)-mediated macrophage pyroptosis plays a critical role in inflammation and host defense. Plasma membrane perforation elicited by caspase-cleaved GSDMD N-terminal domain (GSDMD-NT) triggers membrane rupture and subsequent pyroptotic cell death, resulting in release of pro-inflammatory IL-1β and IL-18. However, the biological processes leading to its membrane translocation and pore formation are not fully understood. Here, using a proteomics approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner and demonstrated that post-translational palmitoylation of GSDMD at Cys191/Cys192 (human/mouse) led to membrane translocation of GSDMD-NT but not full-length GSDMD. GSDMD lipidation, mediated by palmitoyl acyltransferases ZDHHC5/9 and facilitated by LPS-induced reactive oxygen species (ROS), was essential for GSDMD pore-forming activity and pyroptosis. Inhibition of GSDMD palmitoylation with palmitate analog 2-bromopalmitate or a cell permeable GSDMD-specific competing peptide suppressed pyroptosis and IL-1β release in macrophages, mitigated organ damage, and extended the survival of septic mice. Collectively, we establish GSDMD-NT palmitoylation as a key regulatory mechanism controlling GSDMD membrane localization and activation, providing a novel target for modulating immune activity in infectious and inflammatory diseases. One sentence summary: LPS-induced palmitoylation at Cys191/Cys192 is required for GSDMD membrane translocation and its pore-forming activity in macrophages.
Sprache	Englisch
Erscheinungsdatum	2023-02-21
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.02.21.529402
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Heterogeneity of neutrophil spontaneous death.

Teng, Yan / Luo, Hongbo R / Kambara, Hiroto

American journal of hematology

2017 Band 92, Heft 8, Seite(n) E156–E159

Mesh-Begriff(e)	Annexin A5/blood ; Apoptosis ; Cell Death ; Cell Size ; Cellular Senescence ; Coloring Agents ; Flow Cytometry ; Humans ; Neutrophils/cytology ; Propidium ; Stress, Mechanical ; Time-Lapse Imaging
Chemische Substanzen	Annexin A5 ; Coloring Agents ; Propidium (36015-30-2)
Sprache	Englisch
Erscheinungsdatum	2017
Erscheinungsland	United States
Dokumenttyp	Comparative Study ; Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.24764
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis.

Science immunology

2024 Band 9, Heft 94, Seite(n) eadn1452

Abstract: Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a ... ...

Abstract	Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomic approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner. S-palmitoylation of GSDMD at Cys
Mesh-Begriff(e)	Animals ; Humans ; Mice ; Gasdermins ; Lipoylation ; Proteomics ; Pyroptosis
Chemische Substanzen	Gasdermins ; GSDMD protein, human ; Gsdmd protein, mouse
Sprache	Englisch
Erscheinungsdatum	2024-04-12
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.adn1452
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Identification of the Transgene Integration Site and Host Genome Changes in MRP8-Cre/ires-EGFP Transgenic Mice by Targeted Locus Amplification.

Wang, Guan / Zhang, Cunling / Kambara, Hiroto / Dambrot, Cheryl / Xie, Xuemei / Zhao, Li / Xu, Rong / Oneglia, Andrea / Liu, Fei / Luo, Hongbo R

Frontiers in immunology

2022 Band 13, Seite(n) 875991

Abstract: The MRP8-Cre-ires/EGFP transgenic mouse ( ... ...

Abstract	The MRP8-Cre-ires/EGFP transgenic mouse (Mrp8cre
Mesh-Begriff(e)	Animals ; Integrases/genetics ; Internal Ribosome Entry Sites ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Transgenes
Chemische Substanzen	Internal Ribosome Entry Sites ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-)
Sprache	Englisch
Erscheinungsdatum	2022-04-06
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.875991
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics.

Zhang, Xiaoyu / Guo, Rongxia / Kambara, Hiroto / Ma, Fengxia / Luo, Hongbo R

Current opinion in hematology

2018 Band 26, Heft 1, Seite(n) 28–33

Abstract: Purpose of review: CXCR2 is key stimulant of immune cell migration and recruitment, especially of neutrophils. Alleviating excessive neutrophil accumulation and infiltration could prevent prolonged tissue damage in inflammatory disorders. This review ... ...

Abstract	Purpose of review: CXCR2 is key stimulant of immune cell migration and recruitment, especially of neutrophils. Alleviating excessive neutrophil accumulation and infiltration could prevent prolonged tissue damage in inflammatory disorders. This review focuses on recent advances in our understanding of the role of CXCR2 in regulating neutrophil migration and the use of CXCR2 antagonists for therapeutic benefit in inflammatory disorders. Recent findings: Recent studies have provided new insights into how CXCR2 signaling regulates hematopoietic cell mobilization and function in both health and disease. We also summarize several CXCR2 regulatory mechanisms during infection and inflammation such as via Wip1, T-bet, P-selectin glycoprotein ligand-1, granulocyte-colony-stimulating factor, and microbiome. Moreover, we provide an update of studies investigating CXCR2 blockade in the laboratory and in clinical trials. Summary: Neutrophil homeostasis, migration, and recruitment must be precisely regulated. The CXCR2 signaling pathway is a potential target for modifying neutrophil dynamics in inflammatory disorders. We discuss the recent clinical use of CXCR2 antagonists for controlling inflammation.
Mesh-Begriff(e)	Animals ; Anti-Inflammatory Agents/therapeutic use ; Cell Movement/drug effects ; Cell Movement/immunology ; Granulocyte Colony-Stimulating Factor/immunology ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Inflammation/microbiology ; Inflammation/pathology ; Membrane Glycoproteins/immunology ; Microbiota/immunology ; Neutrophils/immunology ; Neutrophils/pathology ; Protein Phosphatase 2C/immunology ; Receptors, Interleukin-8B/antagonists & inhibitors ; Receptors, Interleukin-8B/immunology ; T-Box Domain Proteins/immunology
Chemische Substanzen	Anti-Inflammatory Agents ; CXCR2 protein, human ; Membrane Glycoproteins ; P-selectin ligand protein ; Receptors, Interleukin-8B ; T-Box Domain Proteins ; T-box transcription factor TBX21 ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; PPM1D protein, human (EC 3.1.3.16) ; Protein Phosphatase 2C (EC 3.1.3.16)
Sprache	Englisch
Erscheinungsdatum	2018-11-07
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000476
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages

Xionghui Ding / Hiroto Kambara / Rongxia Guo / Apurva Kanneganti / Maikel Acosta-Zaldívar / Jiajia Li / Fei Liu / Ting Bei / Wanjun Qi / Xuemei Xie / Wenli Han / Ningning Liu / Cunling Zhang / Xiaoyu Zhang / Hongbo Yu / Li Zhao / Fengxia Ma / Julia R. Köhler / Hongbo R. Luo

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Band 24

Abstract: Inflammasome signalling has been shown to protect Candida albicans during infection and as such limits inflammasome inhibitors in this context. Here the authors implicate Gasdermin D in C.ablicans immune evasion and suggests its targeting therapeutically. ...

Abstract	Inflammasome signalling has been shown to protect Candida albicans during infection and as such limits inflammasome inhibitors in this context. Here the authors implicate Gasdermin D in C.ablicans immune evasion and suggests its targeting therapeutically.
Schlagwörter	Science ; Q
Sprache	Englisch
Erscheinungsdatum	2021-11-01T00:00:00Z
Verlag	Nature Portfolio
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel: [Clinical features of tuberculosis among allogeneic hematopoietic stem cell transplantation recipients].

Adachi, Hiroto / Sekiya, Noritaka / Kambara, Yasuhiro / Atsuta, Yuya / Otsuka, Yuki / Konuma, Ryosuke / Suzaki, Ken / Wada, Atsushi / Kishida, Yuya / Uchibori, Yusuke / Mukae, Junichi / Shingai, Naoki / Toya, Takashi / Shimizu, Hiroaki / Najima, Yuho / Kobayashi, Takeshi / Sakamaki, Hisashi / Ohashi, Kazuteru / Doki, Noriko

Rinsho ketsueki] The Japanese journal of clinical hematology

2021 Band 62, Heft 4, Seite(n) 239–244

Abstract: The incidence of tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is 10-40 times higher than that in the general population, which ranges from 0.1% to 5.5%. However, the clinical features of TB among allo- ... ...

Abstract	The incidence of tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is 10-40 times higher than that in the general population, which ranges from 0.1% to 5.5%. However, the clinical features of TB among allo-HSCT recipients in Japan remain unknown. We retrospectively analyzed the incidence of TB and the clinical features of culture-positive TB among allo-HSCT recipients at our hospital between 2002 and 2018. Of 1,047 recipients, 5 (0.4%) developed pulmonary TB (with an incidence rate of 472 per 100,000 population) at a median of 1,730 (range: 586-2,526) days after allo-HSCT. Three patients had chronic graft-versus-host disease upon the onset of TB, which was well-controlled with tacrolimus and/or steroid. Three of five patients completed TB treatment, and the disease did not flare up after therapy completion. The incidence of TB was higher in allo-HSCT recipients than in the general population (0.01%, with an incidence rate of 12.3 per 100,000 population). Therefore, TB should be considered a late complication among allo-HSCT recipients.
Mesh-Begriff(e)	Graft vs Host Disease/epidemiology ; Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Japan/epidemiology ; Retrospective Studies ; Tuberculosis/epidemiology
Sprache	Japanisch
Erscheinungsdatum	2021-03-09
Erscheinungsland	Japan
Dokumenttyp	Journal Article
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.62.239
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages.

Ding, Xionghui / Kambara, Hiroto / Guo, Rongxia / Kanneganti, Apurva / Acosta-Zaldívar, Maikel / Li, Jiajia / Liu, Fei / Bei, Ting / Qi, Wanjun / Xie, Xuemei / Han, Wenli / Liu, Ningning / Zhang, Cunling / Zhang, Xiaoyu / Yu, Hongbo / Zhao, Li / Ma, Fengxia / Köhler, Julia R / Luo, Hongbo R

Nature communications

2021 Band 12, Heft 1, Seite(n) 6699

Abstract: Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome ... ...

Abstract	Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival of Candida-infected mice. Mechanistically, C. albicans hijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventing C. albicans escape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1β production for anti-fungal host defenses. This study demonstrates key functions for GSDMD in Candida's escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target in C. albicans-induced sepsis.
Mesh-Begriff(e)	Animals ; Candida albicans/immunology ; Candida albicans/physiology ; Candidiasis/genetics ; Candidiasis/immunology ; Candidiasis/microbiology ; Caspase 1/genetics ; Caspase 1/immunology ; Caspase 1/metabolism ; Cells, Cultured ; Female ; Host-Pathogen Interactions/immunology ; Humans ; Inflammasomes/genetics ; Inflammasomes/immunology ; Inflammasomes/metabolism ; Interleukin-1beta/immunology ; Interleukin-1beta/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/immunology ; Intracellular Signaling Peptides and Proteins/metabolism ; Kaplan-Meier Estimate ; Kidney/immunology ; Kidney/metabolism ; Kidney/microbiology ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/microbiology ; Mice, Inbred C57BL ; Mice, Knockout ; Phosphate-Binding Proteins/genetics ; Phosphate-Binding Proteins/immunology ; Phosphate-Binding Proteins/metabolism ; Mice
Chemische Substanzen	Gsdmd protein, mouse ; Inflammasomes ; Interleukin-1beta ; Intracellular Signaling Peptides and Proteins ; Phosphate-Binding Proteins ; Caspase 1 (EC 3.4.22.36)
Sprache	Englisch
Erscheinungsdatum	2021-11-18
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27034-9
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection.

Xie, Xuemei / Shi, Qiang / Wu, Peng / Zhang, Xiaoyu / Kambara, Hiroto / Su, Jiayu / Yu, Hongbo / Park, Shin-Young / Guo, Rongxia / Ren, Qian / Zhang, Sudong / Xu, Yuanfu / Silberstein, Leslie E / Cheng, Tao / Ma, Fengxia / Li, Cheng / Luo, Hongbo R

Nature immunology

2020 Band 21, Heft 9, Seite(n) 1119–1133

Abstract: The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here, we profiled >25,000 differentiating and mature mouse neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional ... ...

Abstract	The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here, we profiled >25,000 differentiating and mature mouse neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function and fate decision in their steady state and during bacterial infection. Eight neutrophil populations were defined by distinct molecular signatures. The three mature peripheral blood neutrophil subsets arise from distinct maturing bone marrow neutrophil subsets. Driven by both known and uncharacterized transcription factors, neutrophils gradually acquire microbicidal capability as they traverse the transcriptional landscape, representing an evolved mechanism for fine-tuned regulation of an effective but balanced neutrophil response. Bacterial infection reprograms the genetic architecture of neutrophil populations, alters dynamic transitions between subpopulations and primes neutrophils for augmented functionality without affecting overall heterogeneity. In summary, these data establish a reference model and general framework for studying neutrophil-related disease mechanisms, biomarkers and therapeutic targets at single-cell resolution.
Mesh-Begriff(e)	Animals ; Cell Differentiation ; Cells, Cultured ; Disease Models, Animal ; Escherichia coli/physiology ; Escherichia coli Infections/immunology ; Female ; Gene Expression Profiling ; Homeostasis ; Humans ; Mice ; Neutrophils/physiology ; Peritonitis/immunology ; Sequence Analysis, RNA ; Single-Cell Analysis/methods
Sprache	Englisch
Erscheinungsdatum	2020-07-27
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-020-0736-z
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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