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  1. Artikel ; Online: Evaluation of mucosal-associated invariant T-cells as a potential biomarker to predict infection risk in liver cirrhosis.

    Bengtsson, Bonnie / Maucourant, Christopher / Sandberg, Johan K / Björkström, Niklas K / Hagström, Hannes

    PloS one

    2024  Band 19, Heft 5, Seite(n) e0294695

    Abstract: Background and aims: Infection is a serious complication in patients with cirrhosis. Mucosal-associated invariant T (MAIT) cells are involved in the immune defense against infections and known to be impaired in several chronic conditions, including ... ...

    Abstract Background and aims: Infection is a serious complication in patients with cirrhosis. Mucosal-associated invariant T (MAIT) cells are involved in the immune defense against infections and known to be impaired in several chronic conditions, including cirrhosis. Here, we evaluated if MAIT cell levels in peripheral blood are associated with risk of bacterial infections in patients with cirrhosis.
    Methods: Patients with cirrhosis seen at the Karolinska University Hospital, Stockholm, Sweden, between 2016 and 2019 were included. Levels of MAIT cells in peripheral blood were determined using flow cytometry. Baseline and follow-up data after at least two years of follow-up were collected by chart review for the primary outcome (bacterial infection) and secondary outcomes (decompensation and death). Competing risk and Cox regression were performed.
    Results: We included 106 patients with cirrhosis. The median MAIT cells fraction in the circulation was 0.8% in cirrhosis compared to 6.1% in healthy controls. In contrast to our hypothesis, we found an association in the adjusted analysis between relatively preserved MAIT cell levels, and a slightly higher risk to develop bacterial infections (adjusted subdistribution hazard ratio (aSHR) 1.15 (95%CI = 1.01-1.31). However, MAIT cell levels were not associated with the risk of hepatic decompensation (aSHR 1.19 (95%CI = 0.91-1.56)) nor with death (adjusted hazard ratio 1.10 (95%CI = 0.97-1.22)).
    Conclusions: Relatively preserved MAIT cell levels in blood of patients with cirrhosis were associated with a somewhat higher risk of bacterial infections. The clinical relevance of this might not be strong. MAIT cells might however be an interesting biomarker to explore in future studies.
    Mesh-Begriff(e) Humans ; Mucosal-Associated Invariant T Cells/immunology ; Liver Cirrhosis/immunology ; Liver Cirrhosis/blood ; Liver Cirrhosis/complications ; Male ; Female ; Middle Aged ; Biomarkers/blood ; Bacterial Infections/immunology ; Bacterial Infections/blood ; Bacterial Infections/complications ; Aged ; Sweden/epidemiology ; Adult ; Risk Factors
    Chemische Substanzen Biomarkers
    Sprache Englisch
    Erscheinungsdatum 2024-05-01
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0294695
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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

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

    Viruses

    2019  Band 11, Heft 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-Begriff(e) 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
    Sprache Englisch
    Erscheinungsdatum 2019-01-31
    Erscheinungsland Switzerland
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Comprehensive analysis of early T cell responses to acute Zika Virus infection during the first epidemic in Bahia, Brazil.

    Samri, Assia / Bandeira, Antonio Carlos / Gois, Luana Leandro / Silva, Carlos Gustavo Regis / Rousseau, Alice / Corneau, Aurelien / Tarantino, Nadine / Maucourant, Christopher / Queiroz, Gabriel Andrade Nonato / Vieillard, Vincent / Yssel, Hans / Campos, Gubio Soares / Sardi, Silvia / Autran, Brigitte / Rios Grassi, Maria Fernanda

    PloS one

    2024  Band 19, Heft 5, Seite(n) e0302684

    Abstract: Background: In most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and ... ...

    Abstract Background: In most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and eliminating virus-infected cells during the early stages of infection.
    Aim: To test the hypothesis that circulating T cells exhibit phenotypic and functional activation characteristics during the viremic phase of ZIKV infection.
    Methods: A comprehensive analysis using mass cytometry was performed on peripheral blood mononuclear cells obtained from patients with acute ZIKV infection (as confirmed by RT-PCR) and compared with that from healthy donors (HD). The frequency of IFN-γ-producing T cells in response to peptide pools covering immunogenic regions of structural and nonstructural ZIKV proteins was quantified using an ELISpot assay.
    Results: Circulating CD4+ and CD8+ T lymphocytes from ZIKV-infected patients expressed higher levels of IFN-γ and pSTAT-5, as well as cell surface markers associated with proliferation (Ki-67), activation ((HLA-DR, CD38) or exhaustion (PD1 and CTLA-4), compared to those from HD. Activation of CD4+ and CD8+ memory T cell subsets, including Transitional Memory T Cells (TTM), Effector Memory T cells (TEM), and Effector Memory T cells Re-expressing CD45RA (TEMRA), was prominent among CD4+ T cell subset of ZIKV-infected patients and was associated with increased levels of IFN-γ, pSTAT-5, Ki-67, CTLA-4, and PD1, as compared to HD. Additionally, approximately 30% of ZIKV-infected patients exhibited a T cell response primarily directed against the ZIKV NS5 protein.
    Conclusion: Circulating T lymphocytes spontaneously produce IFN-γ and express elevated levels of pSTAT-5 during the early phase of ZIKV infection whereas recognition of ZIKV antigen results in the generation of virus-specific IFN-γ-producing T cells.
    Mesh-Begriff(e) Humans ; Zika Virus Infection/immunology ; Zika Virus Infection/epidemiology ; Adult ; Zika Virus/immunology ; Female ; Male ; Interferon-gamma/metabolism ; Interferon-gamma/immunology ; Brazil/epidemiology ; CD8-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Middle Aged ; Young Adult ; Epidemics ; Lymphocyte Activation/immunology ; T-Lymphocytes/immunology
    Chemische Substanzen Interferon-gamma (82115-62-6)
    Sprache Englisch
    Erscheinungsdatum 2024-05-09
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0302684
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; 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  Band 50, Heft 3, Seite(n) 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-Begriff(e) Cells, Cultured ; Cytokines/biosynthesis ; Dengue/immunology ; Glycogen Synthase Kinase 3/immunology ; Histocompatibility Antigens Class I/immunology ; Humans ; Killer Cells, Natural/immunology
    Chemische Substanzen Cytokines ; Histocompatibility Antigens Class I ; MHC class I-related chain A ; MICB antigen ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
    Sprache Englisch
    Erscheinungsdatum 2019-12-01
    Erscheinungsland Germany
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; 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  Band 166, Heft 4, Seite(n) 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-Begriff(e) Humans ; Animals ; Mice ; Liver/pathology ; Bile Ducts/pathology ; Biliary Tract/pathology ; Epithelial Cells/pathology ; Cholangitis ; Cell Differentiation ; Cholangitis, Sclerosing/pathology
    Sprache Englisch
    Erscheinungsdatum 2023-11-22
    Erscheinungsland United States
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; 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  Band 30, Heft 3, Seite(n) 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-Begriff(e) 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
    Chemische Substanzen Cytokines
    Sprache Englisch
    Erscheinungsdatum 2020-01-20
    Erscheinungsland France
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; 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.
    Sprache Englisch
    Erscheinungsdatum 2024-02-29
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiae036
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; 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  Band 207, Heft 5, Seite(n) 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-Begriff(e) 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
    Chemische Substanzen KIR3DL1 protein, human ; Receptors, KIR3DL1 ; STAT5 Transcription Factor ; Tumor Necrosis Factor-alpha ; Interleukin-12 (187348-17-0) ; Interferon-gamma (82115-62-6)
    Sprache Englisch
    Erscheinungsdatum 2021-08-18
    Erscheinungsland United States
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; 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  Band 40, Seite(n) 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-Begriff(e) 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
    Chemische Substanzen Antigens, Viral ; Epitopes ; HLA-C Antigens ; KIR2DL2 protein, human ; Receptors, KIR2DL2
    Sprache Englisch
    Erscheinungsdatum 2019-01-30
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2019.01.048
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; 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  Band 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+-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
    Schlagwörter Medicine ; R ; Medicine (General) ; R5-920
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2019-02-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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