AGER-Mediated Lipid Peroxidation Drives Caspase-11 Inflammasome Activation in Sepsis.

Abstract:

:Inflammasome activation can trigger an inflammatory and innate immune response through the release of cytokines and induction of pyroptosis. A dysfunctional inflammasome has been implicated in the development of human pathologies, including sepsis and septic shock. Here, we show that advanced glycosylation end-product specific receptor (AGER/RAGE) is required for caspase-11 inflammasome activation in macrophages. A nuclear damage-associated molecular pattern (nDAMP) complex, including high-mobility group box 1, histone, and DNA, can promote caspase-11-mediated gasdermin D cleavage, interleukin 1β proteolytic maturation, and lactate dehydrogenase release. The inhibition of AGER-mediated lipid peroxidation via arachidonate 5-lipoxygenase (ALOX5) limits caspase-11 inflammasome activation and pyroptosis in macrophages in response to nDAMPs or cytosolic lipopolysaccharide. Importantly, the pharmacologic inhibition of the AGER-ALOX5 pathway or global depletion (Ager-/-) or conditional depletion of AGER in myeloid cells (AgerMye-/-) protects against lipopolysaccharide-induced septic death in poly(I:C)-primed mice. These data identify a molecular basis for caspase-11 inflammasome activation and provide a potential strategy to treat sepsis.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Chen R,Zhu S,Zeng L,Wang Q,Sheng Y,Zhou B,Tang D,Kang R

doi

10.3389/fimmu.2019.01904

subject

Has Abstract

pub_date

2019-08-08 00:00:00

pages

1904

issn

1664-3224

journal_volume

10

pub_type

杂志文章
  • Fli1 Downregulation in Scleroderma Myeloid Cells Has Profibrotic and Proinflammatory Effects.

    abstract::Scleroderma (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. We have previously demonstrated that low Fli1 expression in SSc fibroblasts and endothelial cells plays an important role in SSc pathogenesis. Cells of myeloid and lymphoid origin also expres...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00800

    authors: Bujor AM,El Adili F,Parvez A,Marden G,Trojanowska M

    更新日期:2020-05-19 00:00:00

  • Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota.

    abstract::Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal imm...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01616

    authors: Kaneko K,Akagawa S,Akagawa Y,Kimata T,Tsuji S

    更新日期:2020-07-24 00:00:00

  • Phosphoantigen Presentation to TCR γδ Cells, a Conundrum Getting Less Gray Zones.

    abstract::The mechanistic requirements of antigen recognition by T cells expressing a γδ TCR has revealed important differences with those of αβ TCR cells and, despite impressive new data generated in the very recent years, they remain poorly understood. Based on the structure of the TCR chains and the tissue distribution, γδ c...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00679

    authors: De Libero G,Lau SY,Mori L

    更新日期:2015-01-15 00:00:00

  • Blocking IL-19 Signaling Ameliorates Allergen-Induced Airway Inflammation.

    abstract::Asthma is a chronic inflammatory disease of the airway. Its major symptoms are reversible breathing problems causing airway narrowing and obstruction. IL-19 is a member of the IL-10 family cytokines. We previously showed that IL-19 induces T-helper 2 (Th2) cytokines and that asthma patients had higher serum IL-19 leve...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00968

    authors: Weng YH,Chen WY,Lin YL,Wang JY,Chang MS

    更新日期:2019-04-30 00:00:00

  • Aspergillus fumigatus Infection in Humans With STAT3-Deficiency Is Associated With Defective Interferon-Gamma and Th17 Responses.

    abstract::In humans, loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3) gene is frequently associated with susceptibility to bacterial as well as fungal infections including aspergillosis, although its pathogenesis remains largely unknown. In the present study, we investigated the immune...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00038

    authors: Danion F,Aimanianda V,Bayry J,Duréault A,Wong SSW,Bougnoux ME,Tcherakian C,Alyanakian MA,Guegan H,Puel A,Picard C,Lortholary O,Lanternier F,Latgé JP

    更新日期:2020-01-28 00:00:00

  • A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity.

    abstract::The latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more closely recapitulate i...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00857

    authors: Sherman H,Gitschier HJ,Rossi AE

    更新日期:2018-04-23 00:00:00

  • Isolation of Single-Domain Antibody Fragments That Preferentially Detect Intact (146S) Particles of Foot-and-Mouth Disease Virus for Use in Vaccine Quality Control.

    abstract::Intact (146S) foot-and-mouth disease virus (FMDVs) can dissociate into specific (12S) viral capsid degradation products. FMD vaccines normally consist of inactivated virions. Vaccine quality is dependent on 146S virus particles rather than 12S particles. We earlier isolated two llama single-domain antibody fragments (...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00960

    authors: Harmsen MM,Seago J,Perez E,Charleston B,Eblé PL,Dekker A

    更新日期:2017-08-17 00:00:00

  • Estimating the diversity, completeness, and cross-reactivity of the T cell repertoire.

    abstract::In order to recognize and combat a diverse array of pathogens the immune system has a large repertoire of T cells having unique T cell receptors (TCRs) with only a few clones specific for any given antigen. We discuss how the number of different possible TCRs encoded in the genome (the potential repertoire) and the nu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2013.00485

    authors: Zarnitsyna VI,Evavold BD,Schoettle LN,Blattman JN,Antia R

    更新日期:2013-12-26 00:00:00

  • Impaired Immune Response to Primary but Not to Booster Vaccination Against Hepatitis B in Older Adults.

    abstract::Many current vaccines are less immunogenic and less effective in elderly compared to younger adults due to age-related changes of the immune system. Most vaccines utilized in the elderly contain antigens, which the target population has had previous contact with due to previous vaccination or infection. Therefore, mos...

    journal_title:Frontiers in immunology

    pub_type: 临床试验,杂志文章

    doi:10.3389/fimmu.2018.01035

    authors: Weinberger B,Haks MC,de Paus RA,Ottenhoff THM,Bauer T,Grubeck-Loebenstein B

    更新日期:2018-05-15 00:00:00

  • Novel Mutations of the Tetratricopeptide Repeat Domain 7A Gene and Phenotype/Genotype Comparison.

    abstract::The gastrointestinal tract contains the largest lymphoid organ to react with pathogenic microorganisms and suppress excess inflammation. Patients with primary immunodeficiency diseases (PIDs) can suffer from refractory diarrhea. In this study, we present two siblings who began to suffer from refractory diarrhea with a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01066

    authors: Lien R,Lin YF,Lai MW,Weng HY,Wu RC,Jaing TH,Huang JL,Tsai SF,Lee WI

    更新日期:2017-09-07 00:00:00

  • Mapping the AAV Capsid Host Antibody Response toward the Development of Second Generation Gene Delivery Vectors.

    abstract::The recombinant adeno-associated virus (rAAV) gene delivery system is entering a crucial and exciting phase with the promise of more than 20 years of intense research now realized in a number of successful human clinical trials. However, as a natural host to AAV infection, anti-AAV antibodies are prevalent in the huma...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00009

    authors: Tseng YS,Agbandje-McKenna M

    更新日期:2014-01-30 00:00:00

  • Notch Signaling Pathway Expression in the Skin of Leprosy Patients: Association With Skin and Neural Damage.

    abstract::Introduction: Leprosy is an infectious disease caused by Mycobacterium leprae, a debilitating disease that affects the skin and peripheral nerves. It is possible that tissue changes during infection with leprosy are related to alterations in the activity of the Notch signaling pathway, an innate signaling pathway in t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00368

    authors: Serrano-Coll H,Ospina JP,Salazar-Peláez L,Cardona-Castro N

    更新日期:2020-03-19 00:00:00

  • Role of innate immune response in non-alcoholic Fatty liver disease: metabolic complications and therapeutic tools.

    abstract::Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, both in adults and children. It is characterized by an aberrant lipid storage in hepatocytes, named hepatic steatosis. Simple steatosis remains a benign process in most affected patients, while some of them develop superimp...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00177

    authors: Meli R,Mattace Raso G,Calignano A

    更新日期:2014-04-23 00:00:00

  • Monocyte Subsets: Phenotypes and Function in Tuberculosis Infection.

    abstract::Monocytes are critical defense components that play an important role in the primary innate immune response. The heterogeneous nature of monocytes and their ability to differentiate into either monocyte-derived macrophages or monocyte-derived dendritic cells allows them to serve as a bridge between the innate and adap...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01726

    authors: Sampath P,Moideen K,Ranganathan UD,Bethunaickan R

    更新日期:2018-07-30 00:00:00

  • Computer Simulation of Multi-Color Brainbow Staining and Clonal Evolution of B Cells in Germinal Centers.

    abstract::Clonal evolution of B cells in germinal centers (GCs) is central to affinity maturation of antibodies in response to pathogens. Permanent or tamoxifen-induced multi-color recombination of B cells based on the brainbow allele allows monitoring the degree of color dominance in the course of the GC reaction. Here, we use...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02020

    authors: Meyer-Hermann M,Binder SC,Mesin L,Victora GD

    更新日期:2018-09-25 00:00:00

  • Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis.

    abstract::Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor ery...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01127

    authors: Vivarini ÁC,Calegari-Silva TC,Saliba AM,Boaventura VS,França-Costa J,Khouri R,Dierckx T,Dias-Teixeira KL,Fasel N,Barral AMP,Borges VM,Van Weyenbergh J,Lopes UG

    更新日期:2017-09-15 00:00:00

  • Preferential Reactivity of Dipeptidyl Peptidase-IV Inhibitor-Associated Bullous Pemphigoid Autoantibodies to the Processed Extracellular Domains of BP180.

    abstract::Bullous pemphigoid (BP) is a common autoimmune blistering disease in which autoantibodies target the hemidesmosomal components BP180 and/or BP230 in basal keratinocytes. In BP, 80 to 90% of autoantibodies target the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180. Recently, the administrat...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01224

    authors: Mai Y,Nishie W,Izumi K,Shimizu H

    更新日期:2019-05-29 00:00:00

  • The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

    abstract::T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and ti...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2013.00442

    authors: Collado JA,Guitart C,Ciudad MT,Alvarez I,Jaraquemada D

    更新日期:2013-12-17 00:00:00

  • Anti-PD-1/PD-L1 Blockade Immunotherapy Employed in Treating Hepatitis B Virus Infection-Related Advanced Hepatocellular Carcinoma: A Literature Review.

    abstract::Hepatitis B virus (HBV) infection is regarded as the main etiological risk factor in the process of hepatocellular carcinoma (HCC), as it promotes an immunosuppressive microenvironment that is partially mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway. The tumo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01037

    authors: Li B,Yan C,Zhu J,Chen X,Fu Q,Zhang H,Tong Z,Liu L,Zheng Y,Zhao P,Jiang W,Fang W

    更新日期:2020-05-28 00:00:00

  • Structure Based Refinement of a Humanized Monoclonal Antibody That Targets Tumor Antigen Disialoganglioside GD2.

    abstract::Disialoganglioside GD2 is an important target on several pediatric and adult cancer types including neuroblastoma, retinoblastoma, melanoma, small-cell lung cancer, brain tumors, sarcomas, and cancer stem cells. We have utilized structural and computational methods to refine the framework of humanized monoclonal antib...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2014.00372

    authors: Ahmed M,Hu J,Cheung NK

    更新日期:2014-08-14 00:00:00

  • Allies or Enemies-The Multifaceted Role of Myeloid Cells in the Tumor Microenvironment.

    abstract::For decades, cancer was considered a disease driven by genetic mutations in tumor cells, therefore afflicting a single cell type. This simplified view was slowly replaced by the understanding that interactions between malignant cells and neighboring stromal and immune cells-the tumor microenvironment (TME)-profoundly ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02746

    authors: Haas L,Obenauf AC

    更新日期:2019-11-28 00:00:00

  • Diverse Epitope Specificity, Immunodominance Hierarchy, and Functional Avidity of Effector CD4 T Cells Established During Priming Is Maintained in Lung After Influenza A Virus Infection.

    abstract::One of the major contributions to protective immunity to influenza viruses that is provided by virus-specific CD4 T cells is delivery of effector function to the infected lung. However, there is little known about the selection and breadth of viral epitope-specific CD4 T cells that home to the lung after their initial...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00655

    authors: Richards KA,DiPiazza AT,Rattan A,Knowlden ZAG,Yang H,Sant AJ

    更新日期:2018-04-06 00:00:00

  • Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines.

    abstract::NH36 is a vital enzyme of the DNA metabolism and a specific target for anti-Leishmania chemotherapy. We developed second-generation vaccines composed of the FML complex or its main native antigen, the NH36 nucleoside hydrolase of Leishmania (L.) donovani and saponin, and a DNA vaccine containing the NH36 gene. All the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00813

    authors: Palatnik-de-Sousa CB

    更新日期:2019-04-16 00:00:00

  • Indoleamine 2,3-Dioxygenase 2 Immunohistochemical Expression in Resected Human Non-small Cell Lung Cancer: A Potential New Prognostic Tool.

    abstract::Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage betw...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00839

    authors: Mandarano M,Bellezza G,Belladonna ML,Vannucci J,Gili A,Ferri I,Lupi C,Ludovini V,Falabella G,Metro G,Mondanelli G,Chiari R,Cagini L,Stracci F,Roila F,Puma F,Volpi C,Sidoni A

    更新日期:2020-05-27 00:00:00

  • Sharing CD4+ T Cell Loss: When COVID-19 and HIV Collide on Immune System.

    abstract::COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis. Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outco...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.596631

    authors: Peng X,Ouyang J,Isnard S,Lin J,Fombuena B,Zhu B,Routy JP

    更新日期:2020-12-15 00:00:00

  • Cytokine-Regulation of Na+-K+-Cl- Cotransporter 1 and Cystic Fibrosis Transmembrane Conductance Regulator-Potential Role in Pulmonary Inflammation and Edema Formation.

    abstract::Pulmonary edema, a major complication of lung injury and inflammation, is defined as accumulation of extravascular fluid in the lungs leading to impaired diffusion of respiratory gases. Lung fluid balance across the alveolar epithelial barrier protects the distal airspace from excess fluid accumulation and is mainly r...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00393

    authors: Weidenfeld S,Kuebler WM

    更新日期:2017-04-07 00:00:00

  • Treatment of Pneumococcal Infection by Using Engineered Human C-Reactive Protein in a Mouse Model.

    abstract::C-reactive protein (CRP) binds to several species of bacterial pathogens including Streptococcus pneumoniae. Experiments in mice have revealed that one of the functions of CRP is to protect against pneumococcal infection by binding to pneumococci and activating the complement system. For protection, however, CRP must ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.586669

    authors: Ngwa DN,Singh SK,Gang TB,Agrawal A

    更新日期:2020-10-07 00:00:00

  • Long Non-Coding RNAs Play a Role in the Pathogenesis of Psoriatic Arthritis by Regulating MicroRNAs and Genes Involved in Inflammation and Metabolic Syndrome.

    abstract::Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by inflammation of entheses and synovium, leading to joint erosions and new bone formation. It affects 10-30% of patients with psoriasis, and has an estimated prevalence of approximately 1%. PsA is considered to be primarily an autoimmune disease, d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01533

    authors: Dolcino M,Pelosi A,Fiore PF,Patuzzo G,Tinazzi E,Lunardi C,Puccetti A

    更新日期:2018-07-16 00:00:00

  • Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization.

    abstract::Adjuvanted whole inactivated virus (WIV) influenza vaccines show promise as broadly protective influenza vaccine candidates. Using WIV as basis we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the liposome-based adjuvants CAF01 and CAF09 and the protein-based adjuva...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00646

    authors: Bhide Y,Dong W,Gribonika I,Voshart D,Meijerhof T,de Vries-Idema J,Norley S,Guilfoyle K,Skeldon S,Engelhardt OG,Boon L,Christensen D,Lycke N,Huckriede A

    更新日期:2019-03-29 00:00:00

  • Comparison of Three Immunoassays for the Detection of Myositis Specific Antibodies.

    abstract::Objectives: Standardization of myositis specific antibody (MSA) detection is of high importance because these antibodies are relevant for diagnosis and stratification of patients with idiopathic inflammatory myositis (IIM) and have the potential to be used in classification criteria. Many laboratories rely on immunopr...

    journal_title:Frontiers in immunology

    pub_type: 临床试验,杂志文章

    doi:10.3389/fimmu.2019.00848

    authors: Mahler M,Betteridge Z,Bentow C,Richards M,Seaman A,Chinoy H,McHugh N

    更新日期:2019-04-30 00:00:00