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  1. AU=Keestra-Gounder A. Marijke
  2. AU="María José Endara"
  3. AU="Li, Lin-Zi"
  4. AU="Shirvanian, Moein"
  5. AU="Capaldo, Bianca D"
  6. AU="Matose, Takunda"
  7. AU=Plouffe Brian D.
  8. AU=Kuter David J
  9. AU="Moore, I D"
  10. AU="Schreibing, Felix"
  11. AU=Kang Keunsoo
  12. AU="de Pedro-Múñez, Álvaro"

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  1. Artikel ; Online: Editorial: Inflammasomes in infectious diseases, cell death and ROS generation: stimulation by microorganisms and membrane-derived microvesicles.

    Nagao, Prescilla Emy / Santos, Louisy / Keestra-Gounder, A Marijke

    Frontiers in immunology

    2024  Band 15, Seite(n) 1378506

    Mesh-Begriff(e) Humans ; Inflammasomes/metabolism ; Reactive Oxygen Species/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Cell Death ; Communicable Diseases
    Chemische Substanzen Inflammasomes ; Reactive Oxygen Species ; NLR Family, Pyrin Domain-Containing 3 Protein
    Sprache Englisch
    Erscheinungsdatum 2024-02-27
    Erscheinungsland Switzerland
    Dokumenttyp Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1378506
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation.

    Keestra-Gounder, A Marijke / Nagao, Prescilla Emy

    Frontiers in immunology

    2023  Band 14, Seite(n) 1075834

    Abstract: The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens. Activaton of the receptor ...

    Abstract The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens. Activaton of the receptor leads to formation of the inflammasomes and subsequent processing and activation of caspase-1 that cleaves the proinflammatory cytokines IL-1β and IL-18. Active caspase-1, and in some instances caspase-11, cleaves gasdermin D that translocates to the cell membrane where it forms pores resulting in the cell death program called pyroptosis. Inflammasomes can detect a range of microbial ligands through direct interaction or indirectly through diverse cellular processes including changes in ion fluxes, production of reactive oxygen species and disruption of various host cell functions. In this review, we will focus on the NLRP3, NLRP6, NLRC4 and AIM2 inflammasomes and how they are activated and regulated during infections with Gram-positive bacteria, including
    Mesh-Begriff(e) Inflammasomes/metabolism ; Carrier Proteins/metabolism ; Caspases/metabolism ; Cytokines/metabolism ; Caspase 1/metabolism ; Gram-Positive Bacteria/metabolism
    Chemische Substanzen Inflammasomes ; Carrier Proteins ; Caspases (EC 3.4.22.-) ; Cytokines ; Caspase 1 (EC 3.4.22.36)
    Sprache Englisch
    Erscheinungsdatum 2023-01-24
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1075834
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Nitrate-mediated luminal expansion of

    Sweet, Lydia A / Kuss-Duerkop, Sharon K / Byndloss, Mariana X / Keestra-Gounder, A Marijke

    bioRxiv : the preprint server for biology

    2023  

    Abstract: ... ...

    Abstract Salmonella
    Sprache Englisch
    Erscheinungsdatum 2023-11-03
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.11.03.565559
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells.

    Mendez, Jonathan M / Keestra-Gounder, A Marijke

    Journal of visualized experiments : JoVE

    2020  , Heft 155

    Abstract: The dimeric transcription factor NF-κB regulates many cellular response pathways, including inflammatory pathways by inducing the expression of various cytokines and chemokines. NF-κB is constitutively expressed and is sequestered in the cytosol by the ... ...

    Abstract The dimeric transcription factor NF-κB regulates many cellular response pathways, including inflammatory pathways by inducing the expression of various cytokines and chemokines. NF-κB is constitutively expressed and is sequestered in the cytosol by the inhibitory protein nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα). Activation of NF-κB requires the degradation of IκBα, which then exposes a nuclear localization signal on NF-κB and promotes its trafficking to the nucleus. Once in the nucleus, NF-κB binds to the promotor region of NF-κB target genes such as interleukin 6 (IL-6) and IL-23, to promote their expression. The activation of NF-κB occurs independently of transcription or translation. Therefore, the activation state of NF-κB must be measured either by quantifying NF-κB specifically in the nucleus, or by quantifying expression of NF-κB target genes. In this protocol, cells stably transfected with an NF-κB::luciferase reporter construct are assayed for NF-κB activation using in vitro tissue culture techniques. These cells are infected with Salmonella Typhimurium to activate NF-κB, which traffics to the nucleus and binds to κB sites in the promoter region of luciferase, inducing its expression. Cells are lysed and analyzed with the luciferase assay system. The amount of luciferase produced by the cells correlates with the intensity of the luminescence signal, which is detected by a plate reader. The luminescence signal generated by this procedure provides a quick and highly sensitive method by which to assess NF-κB activation under a range of conditions. This protocol also utilizes quantitative reverse transcription PCR (RT-qPCR) to detect relative mRNA levels that are indicative of gene expression.
    Mesh-Begriff(e) Enzyme Activation ; Gene Expression Regulation ; HeLa Cells ; Humans ; Luciferases/genetics ; Luciferases/metabolism ; Luminescence ; Models, Biological ; NF-kappa B/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Salmonella Infections/genetics ; Salmonella typhimurium/physiology ; Signal Transduction ; Tissue Culture Techniques
    Chemische Substanzen NF-kappa B ; RNA, Messenger ; Luciferases (EC 1.13.12.-)
    Sprache Englisch
    Erscheinungsdatum 2020-01-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/60567
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: NOD1 and NOD2 Activation by Diverse Stimuli: a Possible Role for Sensing Pathogen-Induced Endoplasmic Reticulum Stress.

    Kuss-Duerkop, Sharon K / Keestra-Gounder, A Marijke

    Infection and immunity

    2020  Band 88, Heft 7

    Abstract: Prompt recognition of microbes by cells is critical to eliminate invading pathogens. Some cell-associated pattern recognition receptors (PRRs) recognize and respond to microbial ligands. However, others can respond to cellular perturbations, such as ... ...

    Abstract Prompt recognition of microbes by cells is critical to eliminate invading pathogens. Some cell-associated pattern recognition receptors (PRRs) recognize and respond to microbial ligands. However, others can respond to cellular perturbations, such as damage-associated molecular patterns (DAMPs). Nucleotide oligomerization domains 1 and 2 (NOD1/2) are PRRs that recognize and respond to multiple stimuli of microbial and cellular origin, such as bacterial peptidoglycan, viral infections, parasitic infections, activated Rho GTPases, and endoplasmic reticulum (ER) stress. How NOD1/2 are stimulated by such diverse stimuli is not fully understood but may partly rely on cellular changes during infection that result in ER stress. NOD1/2 are ER stress sensors that facilitate proinflammatory responses for pathogen clearance; thus, NOD1/2 may help mount broad antimicrobial responses through detection of ER stress, which is often induced during a variety of infections. Some pathogens may subvert this response to promote infection through manipulation of NOD1/2 responses to ER stress that lead to apoptosis. Here, we review NOD1/2 stimuli and cellular responses. Furthermore, we discuss pathogen-induced ER stress and how it might potentiate NOD1/2 signaling.
    Mesh-Begriff(e) Animals ; Calcium/metabolism ; Endoplasmic Reticulum Stress/genetics ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Nod1 Signaling Adaptor Protein/genetics ; Nod1 Signaling Adaptor Protein/metabolism ; Nod2 Signaling Adaptor Protein/genetics ; Nod2 Signaling Adaptor Protein/metabolism ; Peptidoglycan/metabolism ; Protein Binding ; Signal Transduction
    Chemische Substanzen Nod1 Signaling Adaptor Protein ; Nod2 Signaling Adaptor Protein ; Peptidoglycan ; Calcium (SY7Q814VUP)
    Sprache Englisch
    Erscheinungsdatum 2020-06-22
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00898-19
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: IRE1α-Driven Inflammation Promotes Clearance of Citrobacter rodentium Infection.

    Sweet, Lydia A / Kuss-Duerkop, Sharon K / Keestra-Gounder, A Marijke

    Infection and immunity

    2021  Band 90, Heft 1, Seite(n) e0048121

    Abstract: Endoplasmic reticulum (ER) stress is intimately linked with inflammation in response to pathogenic infections. ER stress occurs when cells experience a buildup of misfolded or unfolded protein during times of perturbation, such as infections, which ... ...

    Abstract Endoplasmic reticulum (ER) stress is intimately linked with inflammation in response to pathogenic infections. ER stress occurs when cells experience a buildup of misfolded or unfolded protein during times of perturbation, such as infections, which facilitates the unfolded protein response (UPR). The UPR involves multiple host pathways in an attempt to reestablish homeostasis, which oftentimes leads to inflammation and cell death if unresolved. The UPR is activated to help resolve some bacterial infections, and the IRE1α pathway is especially critical in mediating inflammation. To understand the role of the IRE1α pathway of the UPR during enteric bacterial infection, we employed Citrobacter rodentium to study host-pathogen interactions in intestinal epithelial cells and the murine gastrointestinal (GI) tract. C. rodentium is an enteric mouse pathogen that is similar to the human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), for which we have limited small-animal models. Here, we demonstrate that both C. rodentium and EPEC induced the UPR in intestinal epithelial cells. UPR induction during C. rodentium infection correlated with the onset of inflammation in bone marrow-derived macrophages (BMDMs). Our previous work implicated IRE1α and NOD1/2 in ER stress-induced inflammation, which we observed were also required for proinflammatory gene induction during C. rodentium infection. C. rodentium induced IRE1α-dependent inflammation in mice, and inhibiting IRE1α led to a dysregulated inflammatory response and delayed clearance of C. rodentium. This study demonstrates that ER stress aids inflammation and clearance of C. rodentium through a mechanism involving the IRE1α-NOD1/2 axis.
    Mesh-Begriff(e) Animals ; Bacterial Load ; Biomarkers ; Citrobacter rodentium/physiology ; Endoplasmic Reticulum Stress ; Endoribonucleases/genetics ; Endoribonucleases/metabolism ; Enterobacteriaceae Infections/immunology ; Enterobacteriaceae Infections/metabolism ; Enterobacteriaceae Infections/microbiology ; Gene Expression ; Host-Pathogen Interactions/immunology ; Mice ; Nod1 Signaling Adaptor Protein/genetics ; Nod1 Signaling Adaptor Protein/metabolism ; Nod2 Signaling Adaptor Protein/genetics ; Nod2 Signaling Adaptor Protein/metabolism ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction
    Chemische Substanzen Biomarkers ; Nod1 Signaling Adaptor Protein ; Nod1 protein, mouse ; Nod2 Signaling Adaptor Protein ; Nod2 protein, mouse ; Ern1 protein, mouse (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Endoribonucleases (EC 3.1.-)
    Sprache Englisch
    Erscheinungsdatum 2021-11-08
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00481-21
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel: Antimicrobial overproduction sustains intestinal inflammation by inhibiting

    Jang, Kyung Ku / Heaney, Thomas / London, Mariya / Ding, Yi / Yeung, Frank / Ercelen, Defne / Chen, Ying-Han / Axelrad, Jordan / Gurunathan, Sakteesh / Marijke Keestra-Gounder, A / Griffin, Matthew E / Hang, Howard C / Cadwell, Ken

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Loss of antimicrobial proteins such as REG3 family members compromises the integrity of the intestinal barrier. Here, we demonstrate that overproduction of REG3 proteins can also be detrimental by reducing a protective species in the microbiota. Patients ...

    Abstract Loss of antimicrobial proteins such as REG3 family members compromises the integrity of the intestinal barrier. Here, we demonstrate that overproduction of REG3 proteins can also be detrimental by reducing a protective species in the microbiota. Patients with inflammatory bowel disease (IBD) experiencing flares displayed heightened levels of secreted REG3 proteins that mediated depletion of
    Sprache Englisch
    Erscheinungsdatum 2023-02-01
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.01.29.526128
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel: Nf-κb-dependent luciferase activation and quantification of gene expression in Salmonella infected tissue culture cells

    Mendez, Jonathan M / Keestra-Gounder, A. Marijke

    Journal of visualized experiments. 2020 Jan. 12, , no. 155

    2020  

    Abstract: The dimeric transcription factor NF-κB regulates many cellular response pathways, including inflammatory pathways by inducing the expression of various cytokines and chemokines. NF-κB is constitutively expressed and is sequestered in the cytosol by the ... ...

    Abstract The dimeric transcription factor NF-κB regulates many cellular response pathways, including inflammatory pathways by inducing the expression of various cytokines and chemokines. NF-κB is constitutively expressed and is sequestered in the cytosol by the inhibitory protein nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα). Activation of NF-κB requires the degradation of IκBα, which then exposes a nuclear localization signal on NF-κB and promotes its trafficking to the nucleus. Once in the nucleus, NF-κB binds to the promotor region of NF-κB target genes such as interleukin 6 (IL-6) and IL-23, to promote their expression. The activation of NF-κB occurs independently of transcription or translation. Therefore, the activation state of NF-κB must be measured either by quantifying NF-κB specifically in the nucleus, or by quantifying expression of NF-κB target genes. In this protocol, cells stably transfected with an NF-κB::luciferase reporter construct are assayed for NF-κB activation using in vitro tissue culture techniques. These cells are infected with Salmonella Typhimurium to activate NF-κB, which traffics to the nucleus and binds to κB sites in the promoter region of luciferase, inducing its expression. Cells are lysed and analyzed with the luciferase assay system. The amount of luciferase produced by the cells correlates with the intensity of the luminescence signal, which is detected by a plate reader. The luminescence signal generated by this procedure provides a quick and highly sensitive method by which to assess NF-κB activation under a range of conditions. This protocol also utilizes quantitative reverse transcription PCR (RT-qPCR) to detect relative mRNA levels that are indicative of gene expression.
    Schlagwörter B-lymphocytes ; IKappaB kinase ; Salmonella Typhimurium ; chemokines ; cytosol ; gene expression ; genes ; interleukin-23 ; interleukin-6 ; luciferase ; luminescence ; messenger RNA ; nuclear localization signals ; polypeptides ; promoter regions ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; tissue culture ; transcription factor NF-kappa B ; translation (genetics)
    Sprache Englisch
    Erscheinungsverlauf 2020-0112
    Umfang p. e60567.
    Erscheinungsort Journal of Visualized Experiments
    Dokumenttyp Artikel
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/60567
    Datenquelle NAL Katalog (AGRICOLA)

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  9. Artikel ; Online: NOD1 and NOD2: Beyond Peptidoglycan Sensing.

    Keestra-Gounder, A Marijke / Tsolis, Renée M

    Trends in immunology

    2017  Band 38, Heft 10, Seite(n) 758–767

    Abstract: NOD1 and NOD2 are pattern recognition receptors of the innate immune system with well-established roles in sensing fragments of bacterial peptidoglycan. In addition to their role as microbial sensors, recent evidence indicates that nucleotide-binding ... ...

    Abstract NOD1 and NOD2 are pattern recognition receptors of the innate immune system with well-established roles in sensing fragments of bacterial peptidoglycan. In addition to their role as microbial sensors, recent evidence indicates that nucleotide-binding oligomerization domains (NODs) can also recognize a broader array of danger signals. Indeed, recent work has expanded the roles of NOD1 and NOD2 to encompass not only sensing of infections with viruses and parasites but also perceiving perturbations of cellular processes such as regulation of the actin cytoskeleton and maintenance of endoplasmic reticulum homeostasis. This review will comment on recent progress and point out emerging questions in these areas.
    Mesh-Begriff(e) Animals ; Crohn Disease/immunology ; Diabetes Mellitus, Type 2/immunology ; Endoplasmic Reticulum Stress ; Humans ; Nod1 Signaling Adaptor Protein/metabolism ; Nod2 Signaling Adaptor Protein/metabolism ; Obesity/immunology ; Parasites/immunology ; Peptidoglycan ; Signal Transduction ; Viruses/immunology
    Chemische Substanzen Nod1 Signaling Adaptor Protein ; Nod2 Signaling Adaptor Protein ; Peptidoglycan
    Sprache Englisch
    Erscheinungsdatum 2017-08-16
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2017.07.004
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Activation of the Endoplasmic Reticulum Stress Response Impacts the NOD1 Signaling Pathway.

    Mendez, Jonathan M / Kolora, Lakshmi Divya / Lemon, James S / Dupree, Steven L / Keestra-Gounder, A Marijke

    Infection and immunity

    2019  Band 87, Heft 8

    Abstract: Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular pattern recognition receptor (PRR) responsible for sensing bacterial peptidoglycan fragments. Stimulation of NOD1 leads to a robust innate immune response via activation of the major ... ...

    Abstract Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular pattern recognition receptor (PRR) responsible for sensing bacterial peptidoglycan fragments. Stimulation of NOD1 leads to a robust innate immune response via activation of the major transcription factor NF-κB. In addition to peptidoglycan sensing, NOD1 and the closely related PRR NOD2 have been linked to inflammation by responding to the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR). Here we show that differential ER stress induction renders cells more susceptible to
    Mesh-Begriff(e) Animals ; Endoplasmic Reticulum Stress/physiology ; HeLa Cells ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/physiology ; Mice ; NF-kappa B/physiology ; Nod1 Signaling Adaptor Protein/physiology ; RAW 264.7 Cells ; Signal Transduction/physiology ; Unfolded Protein Response ; eIF-2 Kinase/physiology
    Chemische Substanzen Inositol 1,4,5-Trisphosphate Receptors ; NF-kappa B ; NOD1 protein, human ; Nod1 Signaling Adaptor Protein ; EIF2AK3 protein, human (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1)
    Sprache Englisch
    Erscheinungsdatum 2019-07-23
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00826-18
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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