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  1. TI=Impairment of monocytic function after influenza virus infection
  2. AU="Stilgenbauer, Stephan"

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  1. Artikel: Impairment of monocytic function after influenza virus infection.

    Louie, M / Yoo, J / Moran, T / Mayer, L / Sperber, K

    Clinical and diagnostic laboratory immunology

    1995  Band 2, Heft 4, Seite(n) 426–433

    Abstract: ... we investigated monocytic function in macrophage hybridoma cell lines 5 weeks after infection with two strains ... In order to analyze the immunosuppression associated with influenza virus infection ... of influenza virus, X-31 and PR-8. Uniform infection of both cell lines was confirmed by intracytoplasmic staining ...

    Abstract In order to analyze the immunosuppression associated with influenza virus infection, we investigated monocytic function in macrophage hybridoma cell lines 5 weeks after infection with two strains of influenza virus. Clones 30 and 63, chosen for stability in long-term culture, were infected with two strains of influenza virus, X-31 and PR-8. Uniform infection of both cell lines was confirmed by intracytoplasmic staining with the antihemagglutinin strain-specific monoclonal antibodies PY 102 and PY 206. One week after infection, clones 30 and 63 lost their ability to stimulate tetanus toxoid-specific major histocompatibility complex (MHC)-matched responder T cells. Coincident with the inability to stimulate MHC-matched T cells, there was diminished surface expression of class II MHC antigens and LFA-1-alpha and LFA-3 compared with that in uninfected cells: DR, 2.5 versus 10.6% (mean channel 0.3 versus 1.5); DQ, 1.6 versus 15.6% (mean channel 0.3 versus 3.0); DP, 5.0 versus 30.9% (mean channel 0.3 versus 2.0). LFA-1-alpha expression was reduced (13.1 versus 20.0%; mean channel 1.5 versus 2.0) while LFA-3 expression remained the same (22.2 versus 324%; mean channel 3.0 versus 3.3). Class I MHC surface antigen expression was unaltered. Cytokine secretion was also perturbed, as interleukin 1-alpha (IL-1-alpha) and IL-1-beta production was lost 1 week after infection. Production of IL-12 and IL-10 was unchanged, while IL-6 production was increased. The viability of the T cells cocultured with 63Flu was unaltered, demonstrating that the inability of the MHC-restricted T cells to proliferate in response to tetanus toxoid was not due to a toxic effect of 63Flu. Interestingly, other accessory functions, including the ability to support mitogen- and anti-CD3-mediated T-cell proliferation, remained intact. These data suggest that alteration of macrophage function relating to viral infection occurs at multiple levels and may contribute to the immunosuppression observed following influenza virus infection.
    Mesh-Begriff(e) Antigen-Presenting Cells/virology ; CD3 Complex/pharmacology ; CD58 Antigens/metabolism ; Cells, Cultured ; Clone Cells/virology ; Cytokines/biosynthesis ; Histocompatibility Antigens Class I/metabolism ; Histocompatibility Testing ; Humans ; Immune Tolerance ; Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1/metabolism ; Mitogens/pharmacology ; Monocytes/immunology ; Monocytes/virology ; Orthomyxoviridae Infections/immunology ; T-Lymphocytes/immunology ; Tetanus Toxoid/immunology
    Chemische Substanzen CD3 Complex ; CD58 Antigens ; Cytokines ; Histocompatibility Antigens Class I ; Lymphocyte Function-Associated Antigen-1 ; Mitogens ; Tetanus Toxoid
    Sprache Englisch
    Erscheinungsdatum 1995-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1193675-7
    ISSN 1098-6588 ; 1071-412X
    ISSN (online) 1098-6588
    ISSN 1071-412X
    DOI 10.1128/cdli.2.4.426-433.1995
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: The common H232 STING allele shows impaired activities in DNA sensing, susceptibility to viral infection, and in monocyte cell function, while the HAQ variant possesses wild-type properties.

    Froechlich, Guendalina / Finizio, Arianna / Napolano, Alessandra / Amiranda, Sara / De Chiara, Arianna / Pagano, Pasqualina / Mallardo, Massimo / Leoni, Guido / Zambrano, Nicola / Sasso, Emanuele

    Scientific reports

    2023  Band 13, Heft 1, Seite(n) 19541

    Abstract: ... of STING in modulating monocytic cell function and differentiation into macrophages. We further supported ... to clinically relevant viruses, thus supporting a potential contributing cause to differences in inter ... Given the contribution of the STING protein in sensing DNA viruses, bacterial pathogens and misplaced cancer DNA ...

    Abstract Different innate immune pathways converge to Stimulator of interferon genes (STING) and trigger type I interferon responses after recognition of abnormal nucleic acids in the cells. This non-redundant function renders STING a major player in immunosurveillance, and an emerging target for cancer and infectious diseases therapeutics. Beyond somatic mutations that often occur in cancer, the human gene encoding STING protein, TMEM173 (STING1), holds great genetic heterogeneity; R232, HAQ (R71H-G230A-R293Q) and H232 are the most common alleles. Although some of these alleles are likely to be hypomorphic, their function is still debated, due to the available functional assessments, which have been performed in biased biological systems. Here, by using genetic background-matched models, we report on the functional evaluation of R232, HAQ and H232 variants on STING function, and on how these genotypes affect the susceptibility to clinically relevant viruses, thus supporting a potential contributing cause to differences in inter-individual responses to infections. Our findings also demonstrate a novel toll-like receptor-independent role of STING in modulating monocytic cell function and differentiation into macrophages. We further supported the interplay of STING1 variants and human biology by demonstrating how monocytes bearing the H232 allele were impaired in M1/M2 differentiation, interferon response and antigen presentation. Finally, we assessed the response to PD-1 inhibitor in a small cohort of melanoma patients stratified according to STING genotype. Given the contribution of the STING protein in sensing DNA viruses, bacterial pathogens and misplaced cancer DNA, these data may support the development of novel therapeutic options for infectious diseases and cancer.
    Mesh-Begriff(e) Humans ; Alleles ; Communicable Diseases/genetics ; DNA ; Immunity, Innate/genetics ; Interferon Type I/metabolism ; Monocytes/metabolism ; Neoplasms/genetics ; Virus Diseases/genetics
    Chemische Substanzen DNA (9007-49-2) ; Interferon Type I ; STING1 protein, human
    Sprache Englisch
    Erscheinungsdatum 2023-11-09
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-46830-5
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: The common H232 STING allele shows impaired activities in DNA sensing, susceptibility to viral infection, and in monocyte cell function, while the HAQ variant possesses wild-type properties

    Guendalina Froechlich / Arianna Finizio / Alessandra Napolano / Sara Amiranda / Arianna De Chiara / Pasqualina Pagano / Massimo Mallardo / Guido Leoni / Nicola Zambrano / Emanuele Sasso

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Band 16

    Abstract: ... of STING in modulating monocytic cell function and differentiation into macrophages. We further supported ... to clinically relevant viruses, thus supporting a potential contributing cause to differences in inter ... Given the contribution of the STING protein in sensing DNA viruses, bacterial pathogens and misplaced cancer DNA ...

    Abstract Abstract Different innate immune pathways converge to Stimulator of interferon genes (STING) and trigger type I interferon responses after recognition of abnormal nucleic acids in the cells. This non-redundant function renders STING a major player in immunosurveillance, and an emerging target for cancer and infectious diseases therapeutics. Beyond somatic mutations that often occur in cancer, the human gene encoding STING protein, TMEM173 (STING1), holds great genetic heterogeneity; R232, HAQ (R71H-G230A-R293Q) and H232 are the most common alleles. Although some of these alleles are likely to be hypomorphic, their function is still debated, due to the available functional assessments, which have been performed in biased biological systems. Here, by using genetic background-matched models, we report on the functional evaluation of R232, HAQ and H232 variants on STING function, and on how these genotypes affect the susceptibility to clinically relevant viruses, thus supporting a potential contributing cause to differences in inter-individual responses to infections. Our findings also demonstrate a novel toll-like receptor-independent role of STING in modulating monocytic cell function and differentiation into macrophages. We further supported the interplay of STING1 variants and human biology by demonstrating how monocytes bearing the H232 allele were impaired in M1/M2 differentiation, interferon response and antigen presentation. Finally, we assessed the response to PD-1 inhibitor in a small cohort of melanoma patients stratified according to STING genotype. Given the contribution of the STING protein in sensing DNA viruses, bacterial pathogens and misplaced cancer DNA, these data may support the development of novel therapeutic options for infectious diseases and cancer.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-11-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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