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Article ; Online: Control of Acute Arboviral Infection by Natural Killer Cells.

Maucourant, Christopher / Petitdemange, Caroline / Yssel, Hans / Vieillard, Vincent

2019 Volume 11, Issue 2

Abstract: The recent explosive pandemic of chikungunya virus (CHIKV) followed by Zika (ZIKV) virus infections occurring throughout many countries represents the most unexpected arrival of arthropod-borne viral diseases in the past 20 years. Transmitted through the ...

Abstract	The recent explosive pandemic of chikungunya virus (CHIKV) followed by Zika (ZIKV) virus infections occurring throughout many countries represents the most unexpected arrival of arthropod-borne viral diseases in the past 20 years. Transmitted through the bite of
MeSH term(s)	Animals ; Arbovirus Infections/immunology ; Arboviruses/immunology ; Chikungunya Fever/immunology ; Chikungunya virus/immunology ; Coinfection/virology ; Dengue/immunology ; Host Microbial Interactions/immunology ; Humans ; Immunity, Innate ; Killer Cells, Natural/immunology ; Mice ; Zika Virus Infection/immunology
Language	English
Publishing date	2019-01-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v11020131
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Article ; Online: Glycogen synthetase kinase 3 inhibition drives MIC-A/B to promote cytokine production by human natural killer cells in Dengue virus type 2 infection.

Petitdemange, Caroline / Maucourant, Christopher / Tarantino, Nadine / Rey, Juliana / Vieillard, Vincent

European journal of immunology

2019 Volume 50, Issue 3, Page(s) 342–352

Abstract: Dengue virus (DENV) is the most widespread arbovirus worldwide and is responsible for major outbreaks. The host's immune response plays a crucial role in controlling this infection but might also contribute to the promotion of viral spread and ... ...

Abstract	Dengue virus (DENV) is the most widespread arbovirus worldwide and is responsible for major outbreaks. The host's immune response plays a crucial role in controlling this infection but might also contribute to the promotion of viral spread and immunopathology. In response to DENV infection, NK cells preferentially produce cytokines and are cytotoxic in the presence of specific antibodies. Here, we identified that DENV-2 inhibits glycogen synthase kinase 3 (GSK-3) activity to subsequently induce MHC class-1-related chain (MIC) A and MIC-B expression and IL-12 production in monocyte-derived DCs, independently of the STAT-3 pathway. The inhibition of GSK-3 by DENV-2 or small molecules induced MIC-A/B expression on monocyte-derived DCs, resulting in autologous NK cells of a specific increase in IFN-γ and TNF-α production, in the absence of direct cytotoxicity. Together, these findings identified GSK-3 as a regulator of MIC-A/B expression and suggested its role in DENV-2 infection to specifically induce cytokine production by NK cells.
MeSH term(s)	Cells, Cultured ; Cytokines/biosynthesis ; Dengue/immunology ; Glycogen Synthase Kinase 3/immunology ; Histocompatibility Antigens Class I/immunology ; Humans ; Killer Cells, Natural/immunology
Chemical Substances	Cytokines ; Histocompatibility Antigens Class I ; MHC class I-related chain A ; MICB antigen ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
Language	English
Publishing date	2019-12-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201948284
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Cholangiocytes Modulate CD100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation.

Jiang, Xiaojun / Otterdal, Kari / Chung, Brian K / Maucourant, Christopher / Rønneberg, Jørgen D / Zimmer, Christine L / Øgaard, Jonas / Boichuk, Yuliia / Holm, Sverre / Geanon, Daniel / Schneditz, Georg / Bergquist, Annika / Björkström, Niklas K / Melum, Espen

Gastroenterology

2023 Volume 166, Issue 4, Page(s) 667–679

Abstract: Background & aims: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed ... ...

Abstract	Background & aims: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms. Methods: Biopsy specimens of explanted livers and endoscopy-guided sampling were used to assess the CD100 expression by spatial transcriptomics, immune imaging, and high-dimensional flow cytometry. To model pathogenic cholangiocyte-immune cell interaction, splenocytes from mutation-specific mice were cocultured with cholangiocytes. Pathogenic pathways were pinpointed by RNA sequencing analysis of cocultured cells and cross-validated in patient materials. Results: CD100 is mainly expressed by immune cells in the liver and shows a unique pattern around PSC bile ducts with RNA-level colocalization but poor detection at the protein level. This appears to be due to CD100 cleavage as soluble CD100 is increased. Immunophenotyping suggests biliary-infiltrating T cells as the major source of soluble CD100, which is further supported by reduced surface CD100 on T cells and increased metalloproteinases in cholangiocytes after coculturing. Pathogenic T cells that adhered to cholangiocytes up-regulated genes in the T-helper 17 cell differentiation pathway, and the CD100 mutation boosted this process. Consistently, T-helper 17 cells dominate biliary-resident CD4 T cells in patients. Conclusions: CD100 exerts its functional impact through cholangiocyte-immune cell cross talk and underscores an active, proinflammatory role of cholangiocytes that can be relevant to novel treatment approaches.
MeSH term(s)	Humans ; Animals ; Mice ; Liver/pathology ; Bile Ducts/pathology ; Biliary Tract/pathology ; Epithelial Cells/pathology ; Cholangitis ; Cell Differentiation ; Cholangitis, Sclerosing/pathology
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2023.11.283
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Article ; Online: Zika virus in the eye of the cytokine storm.

Maucourant, Christopher / Queiroz, Gabriel Andrade Nonato / Samri, Assia / Grassi, Maria Fernanda Rios / Yssel, Hans / Vieillard, Vincent

European cytokine network

2020 Volume 30, Issue 3, Page(s) 74–81

Abstract: Zika virus (ZIKV) is an emerging arbovirus that causes a mosquito-borne disease. Although infection with ZIKV generally leads to mild disease, its recent emergence in the Americas has been associated with an increase in the development of the Guillain- ... ...

Abstract	Zika virus (ZIKV) is an emerging arbovirus that causes a mosquito-borne disease. Although infection with ZIKV generally leads to mild disease, its recent emergence in the Americas has been associated with an increase in the development of the Guillain-Barré syndrome in adults, as well as with neurological complications, in particular congenital microcephaly, in new-borns. Over the five past years, through the combined efforts of the scientific community, comprehensive remarkable progress aimed at deciphering the clinical, virological, physiopathological, and immunological features of ZIKV infection. This review highlights some of the most recent advances in our understanding of the role of cytokines and chemokines in ZIKV infection, and discusses potential links to pathogenesis.
MeSH term(s)	Americas ; Animals ; Culicidae/immunology ; Culicidae/virology ; Cytokines/immunology ; Eye/immunology ; Eye/virology ; Guillain-Barre Syndrome/immunology ; Humans ; Nervous System Diseases/immunology ; Nervous System Diseases/virology ; Zika Virus/immunology ; Zika Virus Infection/immunology ; Zika Virus Infection/virology
Chemical Substances	Cytokines
Language	English
Publishing date	2020-01-20
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	1118857-1
ISSN	1952-4005 ; 1148-5493
ISSN (online)	1952-4005
ISSN	1148-5493
DOI	10.1684/ecn.2019.0433
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Article ; Online: Type I Interferon Autoantibodies Correlate With Cellular Immune Alterations in Severe COVID-19.

Strunz, Benedikt / Maucourant, Christopher / Mehta, Adi / Wan, Hui / Du, Likun / Sun, Dan / Chen, Puran / Nordlander, Anna / Gao, Yu / Cornillet, Martin / Bister, Jonna / Kvedaraite, Egle / Christ, Wanda / Klingström, Jonas / Geanon, Daniel / Parke, Åsa / Ekwall-Larson, Anna / Rivino, Laura / MacAry, Paul A /

Aleman, Soo / Buggert, Marcus / Ljunggren, Hans-Gustaf / Pan-Hammarström, Qiang / Lund-Johansen, Fridtjof / Strålin, Kristoffer / Björkström, Niklas K

The Journal of infectious diseases

2024

Abstract: Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is ... ...

Abstract	Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). Methods: This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. Results: aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways. Conclusions: Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers.
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae036
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Article ; Online: NK Cell Responses in Zika Virus Infection Are Biased towards Cytokine-Mediated Effector Functions.

Maucourant, Christopher / Nonato Queiroz, Gabriel Andrade / Corneau, Aurelien / Leandro Gois, Luana / Meghraoui-Kheddar, Aida / Tarantino, Nadine / Bandeira, Antonio Carlos / Samri, Assia / Blanc, Catherine / Yssel, Hans / Rios Grassi, Maria Fernanda / Vieillard, Vincent

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 207, Issue 5, Page(s) 1333–1343

Abstract: Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as a global concern because of its impact on human health. ZIKV infection during pregnancy can cause microcephaly and other severe brain defects in the developing fetus and there have been ...

Abstract	Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as a global concern because of its impact on human health. ZIKV infection during pregnancy can cause microcephaly and other severe brain defects in the developing fetus and there have been reports of the occurrence of Guillain-Barré syndrome in areas affected by ZIKV. NK cells are activated during acute viral infections and their activity contributes to a first line of defense because of their ability to rapidly recognize and kill virus-infected cells. To provide insight into NK cell function during ZIKV infection, we have profiled, using mass cytometry, the NK cell receptor-ligand repertoire in a cohort of acute ZIKV-infected female patients. Freshly isolated NK cells from these patients contained distinct, activated, and terminally differentiated, subsets expressing higher levels of CD57, NKG2C, and KIR3DL1 as compared with those from healthy donors. Moreover, KIR3DL1
MeSH term(s)	Acute Disease ; Cells, Cultured ; Cohort Studies ; Female ; Humans ; Interferon-gamma/metabolism ; Interleukin-12/metabolism ; Killer Cells, Natural/immunology ; Lymphocyte Activation ; Pregnancy ; Receptors, KIR3DL1/metabolism ; STAT5 Transcription Factor/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Zika Virus/physiology ; Zika Virus Infection/immunology
Chemical Substances	KIR3DL1 protein, human ; Receptors, KIR3DL1 ; STAT5 Transcription Factor ; Tumor Necrosis Factor-alpha ; Interleukin-12 (187348-17-0) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2001180
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Article ; Online: HLA-C-restricted viral epitopes are associated with an escape mechanism from KIR2DL2

Wauquier, Nadia / Petitdemange, Caroline / Tarantino, Nadine / Maucourant, Christopher / Coomber, Moinya / Lungay, Victor / Bangura, James / Debré, Patrice / Vieillard, Vincent

EBioMedicine

2019 Volume 40, Page(s) 605–613

Abstract: Background: Lassa virus (LASV) is the etiologic agent of an acute hemorrhagic fever endemic in West Africa. Natural killer (NK) cells control viral infections in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and ... ...

Abstract	Background: Lassa virus (LASV) is the etiologic agent of an acute hemorrhagic fever endemic in West Africa. Natural killer (NK) cells control viral infections in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their ligands. LASV infection is associated with defective immune responses, including inhibition of NK cell activity in the presence of MHC-class 1 Methods: We compared individual KIR and HLA-class 1 genotypes of 68 healthy volunteers to 51 patients infected with LASV in Sierra Leone, including 37 survivors and 14 fatalities. Next, potential HLA-C1, HLA-C2, and HLA-Bw4 binding epitopes were in silico screened among LASV nucleoprotein (NP) and envelope glycoprotein (GP). Selected 10-mer peptides were then tested in peptide-HLA stabilization, KIR binding and polyfunction assays. Findings: LASV-infected patients were similar to healthy controls, except for the inhibitory KIR2DL2 gene. We found a specific increase in the HLA-C1:KIR2DL2 interaction in fatalities (10/11) as compared to survivors (12/19) and controls (19/29). We also identified that strong of NP and GP viral epitopes was only observed with HLA-C molecules, and associated with strong inhibition of degranulation in the presence of KIR2DL Interpretation: Our finding suggests that presentation of specific LASV epitopes by HLA-C alleles to the inhibitory KIR2DL2 receptor on NK cells could potentially prevent the killing of infected cells and provides insights into the mechanisms by which LASV can escape NK-cell-mediated immune pressure.
MeSH term(s)	Antigens, Viral/immunology ; Cell Line ; Cytotoxicity, Immunologic ; Epitope Mapping/methods ; Epitopes/immunology ; Genotype ; HLA-C Antigens/genetics ; HLA-C Antigens/immunology ; Humans ; Immune Tolerance ; Immunomodulation ; Immunophenotyping ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Lassa Fever/genetics ; Lassa Fever/immunology ; Lassa Fever/metabolism ; Lassa Fever/virology ; Lassa virus/immunology ; Protein Binding ; Receptors, KIR2DL2/genetics ; Receptors, KIR2DL2/metabolism
Chemical Substances	Antigens, Viral ; Epitopes ; HLA-C Antigens ; KIR2DL2 protein, human ; Receptors, KIR2DL2
Language	English
Publishing date	2019-01-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2019.01.048
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Article ; Online: HLA-C-restricted viral epitopes are associated with an escape mechanism from KIR2DL2+ NK cells in Lassa virus infectionResearch in context

Nadia Wauquier / Caroline Petitdemange / Nadine Tarantino / Christopher Maucourant / Moinya Coomber / Victor Lungay / James Bangura / Patrice Debré / Vincent Vieillard

EBioMedicine, Vol 40, Iss , Pp 605-

2019 Volume 613

Abstract	Background: Lassa virus (LASV) is the etiologic agent of an acute hemorrhagic fever endemic in West Africa. Natural killer (NK) cells control viral infections in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their ligands. LASV infection is associated with defective immune responses, including inhibition of NK cell activity in the presence of MHC-class 1+-infected target cells. Methods: We compared individual KIR and HLA-class 1 genotypes of 68 healthy volunteers to 51 patients infected with LASV in Sierra Leone, including 37 survivors and 14 fatalities. Next, potential HLA-C1, HLA-C2, and HLA-Bw4 binding epitopes were in silico screened among LASV nucleoprotein (NP) and envelope glycoprotein (GP). Selected 10-mer peptides were then tested in peptide-HLA stabilization, KIR binding and polyfunction assays. Findings: LASV-infected patients were similar to healthy controls, except for the inhibitory KIR2DL2 gene. We found a specific increase in the HLA-C1:KIR2DL2 interaction in fatalities (10/11) as compared to survivors (12/19) and controls (19/29). We also identified that strong of NP and GP viral epitopes was only observed with HLA-C molecules, and associated with strong inhibition of degranulation in the presence of KIR2DL+ NK cells. This inhibitory effect significantly increased in the presence of the vGP420 variant, detected in 28.1% of LASV sequences. Interpretation: Our finding suggests that presentation of specific LASV epitopes by HLA-C alleles to the inhibitory KIR2DL2 receptor on NK cells could potentially prevent the killing of infected cells and provides insights into the mechanisms by which LASV can escape NK-cell-mediated immune pressure. Keywords: Lassa virus, NK cells, KIR-L, HLA-C, Viral escape
Keywords	Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: COVID-19-specific metabolic imprint yields insights into multiorgan system perturbations.

Cornillet, Martin / Strunz, Benedikt / Rooyackers, Olav / Ponzetta, Andrea / Chen, Puran / Muvva, Jagadeeswara Rao / Akber, Mira / Buggert, Marcus / Chambers, Benedict J / Dzidic, Majda / Filipovic, Iva / Gorin, Jean-Baptiste / Gredmark-Russ, Sara / Hertwig, Laura / Klingström, Jonas / Kokkinou, Efthymia / Kvedaraite, Egle / Lourda, Magda / Mjösberg, Jenny /

Maucourant, Christopher / Norrby-Teglund, Anna / Parrot, Tiphaine / Perez-Potti, André / Rivera-Ballesteros, Olga / Sandberg, Johan K / Sandberg, John Tyler / Sekine, Takuya / Svensson, Mattias / Varnaite, Renata / Eriksson, Lars I / Aleman, Soo / Strålin, Kristoffer / Ljunggren, Hans-Gustaf / Björkström, Niklas K

European journal of immunology

2021 Volume 52, Issue 3, Page(s) 503–510

Abstract: Corona disease 2019 (COVID-19) affects multiple organ systems. Recent studies have indicated perturbations in the circulating metabolome linked to COVID-19 severity. However, several questions pertain with respect to the metabolome in COVID-19. We ... ...

Abstract	Corona disease 2019 (COVID-19) affects multiple organ systems. Recent studies have indicated perturbations in the circulating metabolome linked to COVID-19 severity. However, several questions pertain with respect to the metabolome in COVID-19. We performed an in-depth assessment of 1129 unique metabolites in 27 hospitalized COVID-19 patients and integrated results with large-scale proteomic and immunology data to capture multiorgan system perturbations. More than half of the detected metabolic alterations in COVID-19 were driven by patient-specific confounding factors ranging from comorbidities to xenobiotic substances. Systematically adjusting for this, a COVID-19-specific metabolic imprint was defined which, over time, underwent a switch in response to severe acute respiratory syndrome coronavirus-2 seroconversion. Integration of the COVID-19 metabolome with clinical, cellular, molecular, and immunological severity scales further revealed a network of metabolic trajectories aligned with multiple pathways for immune activation, and organ damage including neurological inflammation and damage. Altogether, this resource refines our understanding of the multiorgan system perturbations in severe COVID-19 patients.
MeSH term(s)	Adolescent ; Adult ; Aged ; COVID-19/complications ; COVID-19/immunology ; COVID-19/metabolism ; Case-Control Studies ; Central Nervous System Diseases/etiology ; Central Nervous System Diseases/immunology ; Central Nervous System Diseases/metabolism ; Cohort Studies ; Female ; Humans ; Male ; Metabolome/immunology ; Metabolomics ; Middle Aged ; Organ Specificity ; Pandemics ; Phenotype ; Proteomics ; SARS-CoV-2 ; Severity of Illness Index ; Young Adult
Language	English
Publishing date	2021-12-16
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202149626
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Article ; Online: The Karolinska KI/K COVID-19 Immune Atlas: An open resource for immunological research and educational purposes.

Ljunggren, Hans-Gustaf / Ask, Eivind Heggernes / Cornillet, Martin / Strunz, Benedikt / Chen, Puran / Rao Muvva, Jagadeeswara / Akber, Mira / Buggert, Marcus / Chambers, Benedict J / Cuapio, Angelica / Dzidic, Majda / Filipovic, Iva / Flodström-Tullberg, Malin / Garcia, Marina / Gorin, Jean-Baptiste / Gredmark-Russ, Sara / Hertwig, Laura / Klingström, Jonas / Kokkinou, Efthymia /

Scandinavian journal of immunology

2022 , Page(s) e13195

Abstract: The Karolinska KI/K COVID-19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS-CoV-2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response ... ...

Abstract	The Karolinska KI/K COVID-19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS-CoV-2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response towards SARS-CoV-2 infection in humans, as it occurred during the first wave. The Immune Atlas was built as an open resource for broad research and educational purposes. It contains a presentation of the response evoked by different immune and inflammatory cells in defined naïve patient-groups as they presented with moderate and severe COVID-19 disease. The present Resource Article describes how the Karolinska KI/K COVID-19 Immune Atlas allow scientists, students, and other interested parties to freely explore the nature of the immune response towards human SARS-CoV-2 infection in an online setting.
Language	English
Publishing date	2022-06-02
Publishing country	England
Document type	Journal Article
ZDB-ID	120476-2
ISSN	1365-3083 ; 0300-9475
ISSN (online)	1365-3083
ISSN	0300-9475
DOI	10.1111/sji.13195
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