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  1. Article ; Online: Type I and type III interferons: From basic biology and genetics to clinical development for COVID-19 and beyond.

    Andreakos, Evangelos

    Seminars in immunology

    2024  Volume 72, Page(s) 101863

    Abstract: Type I and type III interferons (IFNs) constitute a key antiviral defense systems of the body, inducing viral resistance to cells and mediating diverse innate and adaptive immune functions. Defective type I and type III IFN responses have recently ... ...

    Abstract Type I and type III interferons (IFNs) constitute a key antiviral defense systems of the body, inducing viral resistance to cells and mediating diverse innate and adaptive immune functions. Defective type I and type III IFN responses have recently emerged as the 'Achilles heel' in COVID-19, with such patients developing severe disease and exhibiting a high risk for critical pneumonia and death. Here, we review the biology of type I and type III IFNs, their similarities and important functional differences, and their roles in SARS-CoV-2 infection. We also appraise the various mechanisms proposed to drive defective IFN responses in COVID-19 with particular emphasis to the ability of SARS-CoV-2 to suppress IFN production and activities, the genetic factors involved and the presence of autoantibodies neutralizing IFNs and accounting for a large proportion of individuals with severe COVID-19. Finally, we discuss the long history of the type I IFN therapeutics for the treatment of viral diseases, cancer and multiple sclerosis, the various efforts to use them in respiratory infections, and the newly emerging type III IFN therapeutics, with emphasis to the more recent studies on COVID-19 and their potential use as broad spectrum antivirals for future epidemics or pandemics.
    MeSH term(s) Humans ; COVID-19 ; Interferon Lambda ; SARS-CoV-2 ; Interferon Type I/therapeutic use ; Biology
    Chemical Substances Interferon Lambda ; Interferon Type I
    Language English
    Publishing date 2024-01-24
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2024.101863
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: STINGing type I IFN-mediated immunopathology in COVID-19.

    Andreakos, Evangelos

    Nature immunology

    2022  Volume 23, Issue 4, Page(s) 478–480

    MeSH term(s) COVID-19 ; Humans ; Immunity, Innate ; Interferon-gamma
    Chemical Substances Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2022-03-17
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-022-01174-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Pegylated Interferon Lambda for Covid-19.

    Andreakos, Evangelos / Tsiodras, Sotirios

    The New England journal of medicine

    2023  Volume 388, Issue 22, Page(s) 2107

    MeSH term(s) Humans ; Interferon Lambda ; COVID-19 ; Antiviral Agents/therapeutic use ; Interferons/therapeutic use ; Polyethylene Glycols/therapeutic use
    Chemical Substances Interferon Lambda ; Antiviral Agents ; Interferons (9008-11-1) ; Polyethylene Glycols (3WJQ0SDW1A)
    Language English
    Publishing date 2023-05-31
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2303519
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Comprehensive Analysis of 1-Year-Old Female Apolipoprotein E-Deficient Mice Reveals Advanced Atherosclerosis with Vulnerable Plaque Characteristics.

    Kotsovilis, Sotirios / Salagianni, Maria / Varela, Aimilia / Davos, Constantinos H / Galani, Ioanna E / Andreakos, Evangelos

    International journal of molecular sciences

    2024  Volume 25, Issue 2

    Abstract: Apolipoprotein E-knockout ( ...

    Abstract Apolipoprotein E-knockout (
    MeSH term(s) Female ; Animals ; Mice ; Plaque, Atherosclerotic/diagnostic imaging ; Plaque, Atherosclerotic/genetics ; Plaque, Atherosclerotic/pathology ; Mice, Knockout ; Mice, Knockout, ApoE ; Atherosclerosis/genetics ; Atherosclerosis/pathology ; Necrosis ; Hypercholesterolemia ; Apolipoproteins E/genetics ; Lipids ; Apolipoproteins ; Mice, Inbred C57BL ; Disease Models, Animal
    Chemical Substances Apolipoproteins E ; Lipids ; Apolipoproteins
    Language English
    Publishing date 2024-01-22
    Publishing country Switzerland
    Document type Case Reports ; Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25021355
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Impaired innate antiviral defenses in COVID-19: Causes, consequences and therapeutic opportunities.

    Galani, Ioanna-Evdokia / Andreakos, Evangelos

    Seminars in immunology

    2021  Volume 55, Page(s) 101522

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged pathogen that has caused coronavirus disease 2019 (COVID-19), the worst pandemic of our times leading to tremendous loss of human life and unprecedented measures of social ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged pathogen that has caused coronavirus disease 2019 (COVID-19), the worst pandemic of our times leading to tremendous loss of human life and unprecedented measures of social distancing. COVID-19 symptom manifestations range from asymptomatic disease to severe and lethal outcomes. Lack of previous exposure and immunity to SARS-CoV-2, and high infectivity of the virus have contributed to its broad spread across the globe. In the absence of specific adaptive immunity, innate immune mechanisms are crucial for efficient antiviral defenses and control of the infection. Accumulating evidence now suggests that the remarkable heterogeneity in COVID-19 disease manifestations is due to variable degrees of impairment of innate immune mechanisms. In this review, we summarize recent findings describing both viral and host intrinsic factors that have been linked to defective innate immune responses and account for severe COVID-19. We also discuss emerging therapeutic opportunities for targeting innate immunity for the treatment of COVID-19.
    MeSH term(s) Adaptive Immunity ; Antiviral Agents/therapeutic use ; COVID-19 ; Humans ; Immunity, Innate ; SARS-CoV-2
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2021-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2021.101522
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: COVID-19: lambda interferon against viral load and hyperinflammation.

    Andreakos, Evangelos / Tsiodras, Sotirios

    EMBO molecular medicine

    2020  Volume 12, Issue 6, Page(s) e12465

    Abstract: Coronavirus disease 2019 (COVID-19), triggered by the betacoronavirus SARS-CoV-2, has become one of the worst pandemics of our time that has already caused more than 250,000 deaths (JHU data-05/06/2020, https://coronavirus.jhu.edu/). Effective ... ...

    Abstract Coronavirus disease 2019 (COVID-19), triggered by the betacoronavirus SARS-CoV-2, has become one of the worst pandemics of our time that has already caused more than 250,000 deaths (JHU data-05/06/2020, https://coronavirus.jhu.edu/). Effective therapeutic approaches are urgently needed to reduce the spread of the virus and its death toll. Here, we assess the possibility of using interferon-lambda (IFNλ), a third type of interferon sharing low homology with type I IFNs and IL-10, for treating COVID-19 patients. We discuss the unique role of IFNλ in fine-tuning antiviral immunity in the respiratory tract to achieve optimal protection and minimal host damage and review early evidence that SARS-CoV-2 may impair IFNλ induction, leading to a delayed type I IFN-dominated response that triggers hyperinflammation and severe disease. We also consider the potential windows of opportunity for therapeutic intervention with IFNλ and potential safety considerations. We conclude that IFNλ constitutes a promising therapeutic agent for reducing viral presence and hyperinflammation in a single shot to prevent the devastating consequences of COVID-19 such as pneumonia and acute respiratory distress syndrome (ARDS).
    MeSH term(s) Antiviral Agents/therapeutic use ; Betacoronavirus/isolation & purification ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Coronavirus Infections/virology ; Cytokines/metabolism ; Humans ; Inflammation/etiology ; Interferons/therapeutic use ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/pathology ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Severity of Illness Index ; Viral Load
    Chemical Substances Antiviral Agents ; Cytokines ; Interferons (9008-11-1)
    Keywords covid19
    Language English
    Publishing date 2020-05-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2467145-9
    ISSN 1757-4684 ; 1757-4676
    ISSN (online) 1757-4684
    ISSN 1757-4676
    DOI 10.15252/emmm.202012465
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Protocol for influenza A virus infection of mice and viral load determination.

    Galani, Ioanna-Evdokia / Triantafyllia, Vasiliki / Eleminiadou, Evridiki-Evangelia / Andreakos, Evangelos

    STAR protocols

    2022  Volume 3, Issue 1, Page(s) 101151

    Abstract: Influenza A viruses (IAVs) are common respiratory viruses. Mouse models of IAV infection are valuable to study the mechanisms of IAV infection and pathology. Here, we present a detailed protocol for IAV infection of mice via intranasal administration. We ...

    Abstract Influenza A viruses (IAVs) are common respiratory viruses. Mouse models of IAV infection are valuable to study the mechanisms of IAV infection and pathology. Here, we present a detailed protocol for IAV infection of mice via intranasal administration. We detail the processing of mouse lung tissue and then describe the determination of viral load by several approaches including RNA, protein, or plaque-forming unit assays. This protocol may be adapted to other influenza strains or respiratory viruses. For complete details on the use and execution of this protocol, please refer to Galani et al. (2017).
    MeSH term(s) Humans ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A virus ; Influenza, Human ; Orthomyxoviridae Infections/pathology ; Viral Load
    Language English
    Publishing date 2022-02-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101151
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Notch signaling in adipose tissue macrophages prevents diet-induced inflammation and metabolic dysregulation.

    Siouti, Eleni / Salagianni, Maria / Manioudaki, Maria / Pavlos, Eleftherios / Klinakis, Apostolos / Galani, Ioanna-Evdokia / Andreakos, Evangelos

    European journal of immunology

    2024  , Page(s) e2350669

    Abstract: The importance of macrophages in adipose tissue (AT) homeostasis and inflammation is well established. However, the potential cues that regulate their function remain incompletely understood. To bridge this important gap, we sought to characterize novel ... ...

    Abstract The importance of macrophages in adipose tissue (AT) homeostasis and inflammation is well established. However, the potential cues that regulate their function remain incompletely understood. To bridge this important gap, we sought to characterize novel pathways involved using a mouse model of diet-induced obesity. By performing transcriptomics analysis of AT macrophages (ATMs), we found that late-stage ATMs from high-fat diet mice presented with perturbed Notch signaling accompanied by robust proinflammatory and metabolic changes. To explore the hypothesis that the deregulated Notch pathway contributes to the development of AT inflammation and diet-induced obesity, we employed a genetic approach to abrogate myeloid Notch1 and Notch2 receptors. Our results revealed that the combined loss of Notch1 and Notch2 worsened obesity-related metabolic dysregulation. Body and AT weight gain was higher, blood glucose levels increased and metabolic parameters were substantially worsened in deficient mice fed high-fat diet. Moreover, serum insulin and leptin were elevated as were triglycerides. Molecular analysis of ATMs showed that deletion of Notch receptors escalated inflammation through the induction of an M1-like pro-inflammatory phenotype. Our findings thus support a protective role of myeloid Notch signaling in adipose tissue inflammation and metabolic dysregulation.
    Language English
    Publishing date 2024-02-09
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202350669
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Current Insights into Tissue Injury of Giant Cell Arteritis: From Acute Inflammatory Responses towards Inappropriate Tissue Remodeling.

    Palamidas, Dimitris Anastasios / Chatzis, Loukas / Papadaki, Maria / Gissis, Ilias / Kambas, Konstantinos / Andreakos, Evangelos / Goules, Andreas V / Tzioufas, Athanasios G

    Cells

    2024  Volume 13, Issue 5

    Abstract: Giant cell arteritis (GCA) is an autoimmune disease affecting large vessels in patients over 50 years old. It is an exemplary model of a classic inflammatory disorder with IL-6 playing the leading role. The main comorbidities that may appear acutely or ... ...

    Abstract Giant cell arteritis (GCA) is an autoimmune disease affecting large vessels in patients over 50 years old. It is an exemplary model of a classic inflammatory disorder with IL-6 playing the leading role. The main comorbidities that may appear acutely or chronically are vascular occlusion leading to blindness and thoracic aorta aneurysm formation, respectively. The tissue inflammatory bulk is expressed as acute or chronic delayed-type hypersensitivity reactions, the latter being apparent by giant cell formation. The activated monocytes/macrophages are associated with pronounced Th1 and Th17 responses. B-cells and neutrophils also participate in the inflammatory lesion. However, the exact order of appearance and mechanistic interactions between cells are hindered by the lack of cellular and molecular information from early disease stages and accurate experimental models. Recently, senescent cells and neutrophil extracellular traps have been described in tissue lesions. These structures can remain in tissues for a prolonged period, potentially favoring inflammatory responses and tissue remodeling. In this review, current advances in GCA pathogenesis are discussed in different inflammatory phases. Through the description of these-often overlapping-phases, cells, molecules, and small lipid mediators with pathogenetic potential are described.
    MeSH term(s) Humans ; Middle Aged ; Giant Cell Arteritis/etiology ; Giant Cell Arteritis/pathology ; Inflammation/complications ; Macrophages/pathology ; Neutrophils/pathology ; B-Lymphocytes/pathology
    Language English
    Publishing date 2024-02-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells13050430
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: COVID‐19

    Evangelos Andreakos / Sotirios Tsiodras

    EMBO Molecular Medicine, Vol 12, Iss 6, Pp n/a-n/a (2020)

    lambda interferon against viral load and hyperinflammation

    2020  

    Abstract: Coronavirus disease 2019 (COVID‐19), triggered by the betacoronavirus SARS‐CoV‐2, has become one of the worst pandemics of our time that has already caused more than 250,000 deaths (JHU data‐05/06/2020, https://coronavirus.jhu.edu/). Effective ... ...

    Abstract Coronavirus disease 2019 (COVID‐19), triggered by the betacoronavirus SARS‐CoV‐2, has become one of the worst pandemics of our time that has already caused more than 250,000 deaths (JHU data‐05/06/2020, https://coronavirus.jhu.edu/). Effective therapeutic approaches are urgently needed to reduce the spread of the virus and its death toll. Here, we assess the possibility of using interferon‐lambda (IFNλ), a third type of interferon sharing low homology with type I IFNs and IL‐10, for treating COVID‐19 patients. We discuss the unique role of IFNλ in fine‐tuning antiviral immunity in the respiratory tract to achieve optimal protection and minimal host damage and review early evidence that SARS‐CoV‐2 may impair IFNλ induction, leading to a delayed type I IFN‐dominated response that triggers hyperinflammation and severe disease. We also consider the potential windows of opportunity for therapeutic intervention with IFNλ and potential safety considerations. We conclude that IFNλ constitutes a promising therapeutic agent for reducing viral presence and hyperinflammation in a single shot to prevent the devastating consequences of COVID‐19 such as pneumonia and acute respiratory distress syndrome (ARDS).
    Keywords COVID‐19 ; interferon ; viral infection ; hyperinflammation ; cytokine storm ; Medicine (General) ; R5-920 ; Genetics ; QH426-470 ; covid19
    Subject code 610
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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