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  1. Article ; Online: Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Against SARS-CoV-2 After Natural Infection Is More Potent Than After Vaccination.

    Rieke, Gereon J / van Bremen, Kathrin / Bischoff, Jenny / ToVinh, Michael / Monin, Malte B / Schlabe, Stefan / Raabe, Jan / Kaiser, Kim M / Finnemann, Claudia / Odainic, Alexandru / Kudaliyanage, Anushka / Latz, Eicke / Strassburg, Christian P / Boesecke, Christoph / Schmidt, Susanne V / Krämer, Benjamin / Rockstroh, Jürgen K / Nattermann, Jacob

    The Journal of infectious diseases

    2022  Volume 225, Issue 10, Page(s) 1688–1693

    Abstract: We compared the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific antibodies to induce natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated ... ...

    Abstract We compared the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific antibodies to induce natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated persons. Analyzing plasma samples from 39 coronavirus disease 2019 (COVID-19) patients and 11 vaccinated individuals, significant induction of ADCC could be observed over a period of more than 3 months in both vaccinated and recovered individuals. Although plasma antibody concentrations were lower in recovered patients, we found antibodies elicited by natural infection induced a significantly stronger ADCC response compared to those induced by vaccination, which may affect protection conferred by vaccination.
    MeSH term(s) Antibodies, Neutralizing ; Antibodies, Viral ; Antibody-Dependent Cell Cytotoxicity ; COVID-19/prevention & control ; Humans ; Killer Cells, Natural ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccination
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac060
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Identification and characterization of a hepatic IL-13-producing ILC3-like population potentially involved in liver fibrosis.

    Raabe, Jan / Kaiser, Kim M / ToVinh, Michael / Finnemann, Claudia / Lutz, Philipp / Hoffmeister, Christoph / Bischoff, Jenny / Goeser, Felix / Kaczmarek, Dominik J / Glowka, Tim R / Manekeller, Steffen / Charpentier, Arthur / Langhans, Bettina / Nischalke, Hans Dieter / Toma, Marieta / Strassburg, Christian P / Spengler, Ulrich / Abdallah, Ali T / Krämer, Benjamin /
    Nattermann, Jacob

    Hepatology (Baltimore, Md.)

    2023  Volume 78, Issue 3, Page(s) 787–802

    Abstract: Background and aims: Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its ... ...

    Abstract Background and aims: Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its potential role in chronic liver disease. Here, we performed a detailed characterization of intrahepatic ILCs in both healthy and fibrotic livers.
    Approach and results: A total of 50 livers (nonfibrotic = 22, and fibrotic = 29) were analyzed and compared with colon and tonsil tissue (each N = 14) and peripheral blood (N = 32). Human intrahepatic ILCs were characterized ex vivo and on stimulation using flow cytometry and single-cell RNA sequencing. ILC differentiation and plasticity were analyzed by both bulk and clonal expansion experiments. Finally, the effects of ILC-derived cytokines on primary human HSteCs were studied. Unexpectedly, we found that an "unconventional" ILC3-like cell represented the major IL-13-producing liver ILC subset. IL-13 + ILC3-like cells were specifically enriched in the human liver, and increased frequencies of this cell type were found in fibrotic livers. ILC3-derived IL-13 production induced upregulation of proinflammatory genes in HSteCs, indicating a potential role in the regulation of hepatic fibrogenesis. Finally, we identified KLRG1-expressing ILC precursors as the potential progenitor of hepatic IL-13 + ILC3-like cells.
    Conclusions: We identified a formerly undescribed subset of IL-13-producing ILC3-like cells that is enriched in the human liver and may be involved in the modulation of chronic liver disease.
    MeSH term(s) Humans ; Interleukin-13/metabolism ; Lymphocytes ; Immunity, Innate ; Liver Cirrhosis/metabolism
    Chemical Substances Interleukin-13
    Language English
    Publishing date 2023-04-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1097/HEP.0000000000000350
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mitochondrial Dysfunction Contributes to Impaired Cytokine Production of CD56bright Natural Killer Cells From Human Immunodeficiency Virus-Infected Individuals Under Effective Antiretroviral Therapy.

    ToVinh, Michael / Hörr, Gregor / Dobrikova, Kristiyana / Gotter, Christina / Rommel, Clemens / Hoffmeister, Christoph / Raabe, Jan / Kaiser, Kim M / Finnemann, Claudia / Bischoff, Jenny / Rieke, Gereon J / Wilhelm, Christoph / Schmitt, Vanessa / Möhl, Christoph / Aghabeig, Mansoureh / Schwarze-Zander, Carolynne / Boesecke, Christoph / van Bremen, Kathrin / Wasmuth, Jan Christian /
    Strassburg, Christian P / Rockstroh, Jürgen K / Spengler, Ulrich / Krämer, Benjamin / Nattermann, Jacob

    The Journal of infectious diseases

    2022  Volume 226, Issue 5, Page(s) 901–906

    Abstract: Human immunodeficiency virus (HIV) infection is associated with impaired natural killer (NK) cell activity, which is only incompletely restored under antiretroviral therapy. Analyzing the bioenergetics profiles of oxygen consumption, we observed that ... ...

    Abstract Human immunodeficiency virus (HIV) infection is associated with impaired natural killer (NK) cell activity, which is only incompletely restored under antiretroviral therapy. Analyzing the bioenergetics profiles of oxygen consumption, we observed that several parameters were significantly reduced in HIV+ NK cells, indicating a mitochondrial defect. Accordingly, we found HIV+ CD56bright NK cells to display a decreased mitochondrial membrane potential and mitochondrial mass. Both parameters were positively correlated with interferon gamma (IFN-γ) production of NK cells. Finally, we demonstrated that stimulation of HIV+ NK cells with MitoTEMPO, a mitochondria-targeting antioxidant, significantly improved IFN-γ production. We identified mitochondrial dysfunction as a mechanism that contributes to impaired NK cell function.
    MeSH term(s) CD56 Antigen/metabolism ; Cytokines/metabolism ; HIV/metabolism ; HIV Infections/complications ; Humans ; Killer Cells, Natural/metabolism ; Mitochondria/metabolism
    Chemical Substances CD56 Antigen ; Cytokines
    Language English
    Publishing date 2022-03-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac103
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  4. Article ; Online: N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection.

    Shan, Dandan / Johnson, Joseph M / Fernandes, Syrena C / Suib, Hannah / Hwang, Soyoon / Wuelfing, Danica / Mendes, Muriel / Holdridge, Marcella / Burke, Elaine M / Beauregard, Katie / Zhang, Ying / Cleary, Megan / Xu, Samantha / Yao, Xiao / Patel, Purvish P / Plavina, Tatiana / Wilson, David H / Chang, Lei / Kaiser, Kim M /
    Nattermann, Jacob / Schmidt, Susanne V / Latz, Eicke / Hrusovsky, Kevin / Mattoon, Dawn / Ball, Andrew J

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 1931

    Abstract: The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly ... ...

    Abstract The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva. In all matrices in the studies conducted to date we observe >98% negative percent agreement and >90% positive percent agreement with molecular testing for days 1-7 in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals. N-protein load decreases as anti-SARS-CoV-2 spike-IgG increases, and N-protein levels correlate with RT-PCR Ct-values in saliva, and between matched saliva and capillary blood samples. This Simoa SARS-CoV-2 N-protein assay effectively detects SARS-CoV-2 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at home and point of care sample collection.
    MeSH term(s) COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/virology ; COVID-19 Testing/methods ; Coronavirus Nucleocapsid Proteins/blood ; Coronavirus Nucleocapsid Proteins/genetics ; Epidemics ; Home Care Services ; Humans ; Point-of-Care Systems ; ROC Curve ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; SARS-CoV-2/physiology ; Saliva/virology ; Specimen Handling/methods
    Chemical Substances Coronavirus Nucleocapsid Proteins
    Language English
    Publishing date 2021-03-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-22072-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: HIV-Associated Microbial Translocation May Affect Cytokine Production of CD56bright NK Cells via Stimulation of Monocytes.

    ToVinh, Michael / Hörr, Gregor / Hoffmeister, Christoph / Dobrikova, Kristiyana / Gotter, Christina / Raabe, Jan / Kaiser, Kim M / Ahmad, Sarah / Finnemann, Claudia / Matejec, Eyleen / Hack, Gudrun / Bischoff, Jenny / Rieke, Gereon J / Schwarze-Zander, Carolynne / Boesecke, Christoph / van Bremen, Kathrin / Wasmuth, Jan-Christian / Eis-Hübinger, Anna M / Streeck, Hendrik /
    Verhasselt, Hedda L / Oldenburg, Johannes / Strassburg, Christian P / Rockstroh, Jürgen K / Spengler, Ulrich / Krämer, Benjamin / Nattermann, Jacob

    The Journal of infectious diseases

    2022  Volume 227, Issue 4, Page(s) 577–582

    Abstract: The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a ...

    Abstract The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a marker for microbial translocation. Both IFABP and LBP plasma concentrations were inversely correlated with NK cell interferon-γ production, suggesting microbial translocation to modulate NK cell functions. Accordingly, we found lipopolysaccharide to have an indirect inhibitory effect on NK cells via triggering monocytes' transforming growth factor-β production. Taken together, our data suggest increased microbial translocation to be involved in HIV-associated NK cell dysfunction.
    MeSH term(s) Humans ; Cytokines ; HIV Infections/metabolism ; HIV Infections/microbiology ; Killer Cells, Natural/metabolism ; Killer Cells, Natural/microbiology ; Killer Cells, Natural/pathology ; Monocytes ; CD56 Antigen ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology
    Chemical Substances Cytokines ; CD56 Antigen ; lipopolysaccharide-binding protein
    Language English
    Publishing date 2022-12-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac485
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Single-cell RNA sequencing identifies a population of human liver-type ILC1s.

    Krämer, Benjamin / Nalin, Ansel P / Ma, Feiyang / Eickhoff, Sarah / Lutz, Philipp / Leonardelli, Sonia / Goeser, Felix / Finnemann, Claudia / Hack, Gudrun / Raabe, Jan / ToVinh, Michael / Ahmad, Sarah / Hoffmeister, Christoph / Kaiser, Kim M / Manekeller, Steffen / Branchi, Vittorio / Bald, Tobias / Hölzel, Michael / Hüneburg, Robert /
    Nischalke, Hans Dieter / Semaan, Alexander / Langhans, Bettina / Kaczmarek, Dominik J / Benner, Brooke / Lordo, Matthew R / Kowalski, Jesse / Gerhardt, Adam / Timm, Jörg / Toma, Marieta / Mohr, Raphael / Türler, Andreas / Charpentier, Arthur / van Bremen, Tobias / Feldmann, Georg / Sattler, Arne / Kotsch, Katja / Abdallah, Ali T / Strassburg, Christian P / Spengler, Ulrich / Carson, William E / Mundy-Bosse, Bethany L / Pellegrini, Matteo / O'Sullivan, Timothy E / Freud, Aharon G / Nattermann, Jacob

    Cell reports

    2023  Volume 42, Issue 1, Page(s) 111937

    Abstract: Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of ... ...

    Abstract Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a
    MeSH term(s) Humans ; Lymphocytes ; Immunity, Innate ; Endothelial Cells ; Killer Cells, Natural ; Liver ; Transcription Factors ; Sequence Analysis, RNA
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2023-01-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2022.111937
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  7. Article ; Online: SARS-Coronavirus-2 nucleocapsid protein measured in blood using a Simoa ultra-sensitive immunoassay differentiates COVID-19 infection with high clinical sensitivity.

    Shan, Dandan / Johnson, Joseph M / Fernandes, Syrena C / Mendes, Muriel / Suib, Hannah / Holdridge, Marcella / Burke, Elaine M / Beauregard, Katie G / Zhang, Ying / Cleary, Megan / Xu, Samantha / Yao, Xiao / Patel, Purvish P / Plavina, Tatiana / Wilson, David H / Chang, Lei / Kaiser, Kim M / Natterman, Jacob / Schmidt, Susanne V /
    Latz, Eicke / Hrusovsky, Kevin / Mattoon, Dawn / Ball, Andrew J

    medRxiv

    Abstract: The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. Despite rapid advances in diagnostic test development and scale-up, there remains an ongoing need for SARS-CoV-2 tests which are highly sensitive, ... ...

    Abstract The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. Despite rapid advances in diagnostic test development and scale-up, there remains an ongoing need for SARS-CoV-2 tests which are highly sensitive, specific, minimally invasive, cost-effective and scalable for broad testing and surveillance. Here we report development of a highly sensitive single molecule array (Simoa) immunoassay on the automated HD-X platform for the detection of SARS-CoV-2 Nucleocapsid protein (N-protein) in venous and capillary blood (fingerstick). In pre-pandemic and clinical sample sets, the assay has 100% specificity and 97.4% sensitivity for serum / plasma samples. The limit of detection (LoD) estimated by titration of inactivated SARS-CoV-2 virus is 0.2 pg/ml, corresponding to 0.05 Median Tissue Culture Infectious Dose (TCID50) per ml, > 2000 times more sensitive than current EUA approved antigen tests. No cross-reactivity to other common respiratory viruses, including hCoV229E, hCoVOC43, hCoVNL63, Influenza A or Influenza B, was observed. We detected elevated N-protein concentrations in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals using capillary blood from a finger-stick collection device. The Simoa SARS-CoV-2 N-protein assay has the potential to detect COVID-19 infection via antigen in blood with similar or better performance characteristics of molecular tests, while also enabling at home and point of care sample collection.
    Keywords covid19
    Language English
    Publishing date 2020-08-17
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.08.14.20175356
    Database COVID19

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