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  1. Article ; Online: A complex immune communication between eicosanoids and pulmonary macrophages.

    Pernet, Erwan / Poschmann, Jeremie / Divangahi, Maziar

    Current opinion in virology

    2024  Volume 66, Page(s) 101399

    Abstract: Respiratory viral infections represent a constant threat for human health and urge for a better understanding of the pulmonary immune response to prevent disease severity. Macrophages are at the center of pulmonary immunity, where they play a pivotal ... ...

    Abstract Respiratory viral infections represent a constant threat for human health and urge for a better understanding of the pulmonary immune response to prevent disease severity. Macrophages are at the center of pulmonary immunity, where they play a pivotal role in orchestrating beneficial and/or pathological outcomes during infection. Eicosanoids, the host bioactive lipid mediators, have re-emerged as important regulators of pulmonary immunity during respiratory viral infections. In this review, we summarize the current knowledge linking eicosanoids' and pulmonary macrophages' homeostatic and antimicrobial functions and discuss eicosanoids as emerging targets for immunotherapy in viral infection.
    Language English
    Publishing date 2024-03-27
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2024.101399
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  2. Article ; Online: Modulation of Airway Expression of the Host Bactericidal Enzyme, sPLA2-IIA, by Bacterial Toxins.

    Wu, Yongzheng / Pernet, Erwan / Touqui, Lhousseine

    Toxins

    2023  Volume 15, Issue 7

    Abstract: Host molecules with antimicrobial properties belong to a large family of mediators including type-IIA secreted phospholipase A2 (sPLA2-IIA). The latter is a potent bactericidal agent with high selectivity against Gram-positive bacteria, but it may also ... ...

    Abstract Host molecules with antimicrobial properties belong to a large family of mediators including type-IIA secreted phospholipase A2 (sPLA2-IIA). The latter is a potent bactericidal agent with high selectivity against Gram-positive bacteria, but it may also play a role in modulating the host inflammatory response. However, several pathogen-associated molecular patterns (PAMPs) or toxins produced by pathogenic bacteria can modulate the levels of sPLA2-IIA by either inducing or inhibiting its expression in host cells. Thus, the final sPLA2-IIA concentration during the infection process is determined by the orchestration between the levels of toxins that stimulate and those that downregulate the expression of this enzyme. The stimulation of sPLA2-IIA expression is a process that participates in the clearance of invading bacteria, while inhibition of this expression highlights a mechanism by which certain bacteria can subvert the immune response and invade the host. Here, we will review the major functions of sPLA2-IIA in the airways and the role of bacterial toxins in modulating the expression of this enzyme. We will also summarize the major mechanisms involved in this modulation and the potential consequences for the pulmonary host response to bacterial infection.
    MeSH term(s) Phospholipases A2, Secretory ; Bacterial Toxins ; Anti-Bacterial Agents/pharmacology ; Group II Phospholipases A2
    Chemical Substances Phospholipases A2, Secretory (EC 3.1.1.4) ; Bacterial Toxins ; Anti-Bacterial Agents ; Group II Phospholipases A2 (EC 3.1.1.4)
    Language English
    Publishing date 2023-07-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins15070440
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  3. Article ; Online: Training can't always lead to Olympic macrophages.

    Pernet, Erwan / Prevel, Renaud / Divangahi, Maziar

    The Journal of clinical investigation

    2022  Volume 132, Issue 7

    Abstract: Although the memory capacity of innate immune cells, termed trained immunity (TI), is a conserved evolutionary trait, the cellular and molecular mechanisms involved are incompletely understood. One fundamental question is whether the induction of TI ... ...

    Abstract Although the memory capacity of innate immune cells, termed trained immunity (TI), is a conserved evolutionary trait, the cellular and molecular mechanisms involved are incompletely understood. One fundamental question is whether the induction of TI generates a homogeneous or heterogeneous population of trained cells. In this issue of the JCI, Zhang, Moorlag, and colleagues tackle this question by combining an in vitro model system of TI with single-cell RNA sequencing. The induction of TI in human monocytes resulted in three populations with distinct transcriptomic profiles. Interestingly, the presence of lymphocytes in the microenvironment of monocytes substantially impacted TI. The authors also identified a similar population of monocytes in various human diseases or in individuals vaccinated with bacillus Calmette-Guérin. These insights warrant in-depth analysis of TI in responsive versus nonresponsive immune cells and suggest that modulating TI may provide a strategy for treating infections and inflammatory diseases.
    MeSH term(s) Humans ; Immunity, Innate ; Leukocyte Count ; Macrophages ; Monocytes ; Mycobacterium bovis
    Language English
    Publishing date 2022-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI158468
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  4. Article ; Online: Author Correction: BCG immunization induces CX3CR1

    Tran, Kim A / Pernet, Erwan / Sadeghi, Mina / Downey, Jeffrey / Chronopoulos, Julia / Lapshina, Elizabeth / Tsai, Oscar / Kaufmann, Eva / Ding, Jun / Divangahi, Maziar

    Nature immunology

    2024  Volume 25, Issue 3, Page(s) 578

    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-024-01773-5
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    Zs.A 5294: Show issues Location:
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  5. Article ; Online: BCG immunization induces CX3CR1

    Tran, Kim A / Pernet, Erwan / Sadeghi, Mina / Downey, Jeffrey / Chronopoulos, Julia / Lapshina, Elizabeth / Tsai, Oscar / Kaufmann, Eva / Ding, Jun / Divangahi, Maziar

    Nature immunology

    2024  Volume 25, Issue 3, Page(s) 418–431

    Abstract: After a century of using the Bacillus Calmette-Guérin (BCG) vaccine, our understanding of its ability to provide protection against homologous (Mycobacterium tuberculosis) or heterologous (for example, influenza virus) infections remains limited. Here we ...

    Abstract After a century of using the Bacillus Calmette-Guérin (BCG) vaccine, our understanding of its ability to provide protection against homologous (Mycobacterium tuberculosis) or heterologous (for example, influenza virus) infections remains limited. Here we show that systemic (intravenous) BCG vaccination provides significant protection against subsequent influenza A virus infection in mice. We further demonstrate that the BCG-mediated cross-protection against influenza A virus is largely due to the enrichment of conventional CD4
    MeSH term(s) Animals ; Mice ; Administration, Intravenous ; BCG Vaccine/immunology ; Influenza A virus ; Memory T Cells ; Trained Immunity ; Vaccination ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/prevention & control
    Chemical Substances BCG Vaccine
    Language English
    Publishing date 2024-01-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01739-z
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  6. Article ; Online: Dissecting host cell death programs in the pathogenesis of influenza.

    Downey, Jeffrey / Pernet, Erwan / Coulombe, François / Divangahi, Maziar

    Microbes and infection

    2018  Volume 20, Issue 9-10, Page(s) 560–569

    Abstract: Influenza A virus (IAV) is a pulmonary pathogen, responsible for significant yearly morbidity and mortality. Due to the absence of highly effective antiviral therapies and vaccine, as well as the constant threat of an emerging pandemic strain, there is ... ...

    Abstract Influenza A virus (IAV) is a pulmonary pathogen, responsible for significant yearly morbidity and mortality. Due to the absence of highly effective antiviral therapies and vaccine, as well as the constant threat of an emerging pandemic strain, there is considerable need to better understand the host-pathogen interactions and the factors that dictate a protective versus detrimental immune response to IAV. Even though evidence of IAV-induced cell death in human pulmonary epithelial and immune cells has been observed for almost a century, very little is known about the consequences of cell death on viral pathogenesis. Recent study indicates that both the type of cell death program and its kinetics have major implications on host defense and survival. In this review, we discuss advances in our understanding of cell death programs during influenza virus infection, in hopes of fostering new areas of investigation for targeted clinical intervention.
    MeSH term(s) Alveolar Epithelial Cells/pathology ; Animals ; Cell Death ; Host-Pathogen Interactions/immunology ; Humans ; Influenza A virus/physiology ; Influenza, Human/immunology ; Kinetics ; Macrophages, Alveolar/pathology ; Orthomyxoviridae Infections/immunology
    Keywords covid19
    Language English
    Publishing date 2018-04-18
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1465093-9
    ISSN 1769-714X ; 1286-4579
    ISSN (online) 1769-714X
    ISSN 1286-4579
    DOI 10.1016/j.micinf.2018.03.005
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  7. Article ; Online: Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against influenza virus.

    Downey, Jeffrey / Randolph, Haley E / Pernet, Erwan / Tran, Kim A / Khader, Shabaana A / King, Irah L / Barreiro, Luis B / Divangahi, Maziar

    Cell reports

    2022  Volume 39, Issue 12, Page(s) 110974

    Abstract: Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be ... ...

    Abstract Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be countered by largely uncharacterized disease tolerance mechanisms. Here, we show that mitochondrial cyclophilin D (CypD) protects against IAV via disease tolerance. CypD
    MeSH term(s) Animals ; Peptidyl-Prolyl Isomerase F ; Humans ; Influenza A virus ; Influenza, Human ; Interleukins ; Killer Cells, Natural ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Orthomyxoviridae Infections ; Interleukin-22
    Chemical Substances Peptidyl-Prolyl Isomerase F ; Interleukins
    Language English
    Publishing date 2022-06-19
    Publishing country United States
    Document type Journal Article ; 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.2022.110974
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  8. Article ; Online: Human alveolar macrophage metabolism is compromised during

    Mendonca, Laura E / Pernet, Erwan / Khan, Nargis / Sanz, Joaquin / Kaufmann, Eva / Downey, Jeffrey / Grant, Alexandre / Orlova, Marianna / Schurr, Erwin / Krawczyk, Connie / Jones, Russell G / Barreiro, Luis B / Divangahi, Maziar

    Frontiers in immunology

    2023  Volume 13, Page(s) 1044592

    Abstract: Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain ... ...

    Abstract Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of
    MeSH term(s) Humans ; Animals ; Mice ; Macrophages, Alveolar/metabolism ; Tuberculosis/microbiology ; Mycobacterium tuberculosis ; Macrophages/microbiology ; Necrosis/metabolism
    Language English
    Publishing date 2023-01-26
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1044592
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  9. Article ; Online: Leukotriene B

    Pernet, Erwan / Downey, Jeffrey / Vinh, Donald C / Powell, William S / Divangahi, Maziar

    Nature microbiology

    2019  Volume 4, Issue 8, Page(s) 1389–1400

    Abstract: Host defence against influenza A virus (IAV) infection depends not only on host resistance to eliminate the virus, but also disease tolerance to limit lung tissue damage and maintain pulmonary function. Fatal IAV infections are frequently the result of a ...

    Abstract Host defence against influenza A virus (IAV) infection depends not only on host resistance to eliminate the virus, but also disease tolerance to limit lung tissue damage and maintain pulmonary function. Fatal IAV infections are frequently the result of a maladaptive immune response that compromises disease tolerance rather than host resistance to infection. Here, we show that the leukotriene B
    MeSH term(s) Animals ; Cell Death ; Cell Line ; Cell Proliferation ; Humans ; Immune Tolerance ; Immunity, Innate/immunology ; Influenza A virus/immunology ; Influenza, Human/immunology ; Influenza, Human/pathology ; Interferon Type I/metabolism ; Leukotriene B4/metabolism ; Lung/immunology ; Lung/pathology ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Orthomyxoviridae Infections/immunology ; Receptor, Interferon alpha-beta/genetics ; Receptor, Interferon alpha-beta/metabolism ; Receptors, CCR2/genetics ; STAT1 Transcription Factor/metabolism ; Signal Transduction
    Chemical Substances Ccr2 protein, mouse ; Interferon Type I ; Receptors, CCR2 ; STAT1 Transcription Factor ; Stat1 protein, mouse ; Receptor, Interferon alpha-beta (156986-95-7) ; Leukotriene B4 (1HGW4DR56D)
    Keywords covid19
    Language English
    Publishing date 2019-05-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-019-0444-3
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  10. Article ; Online: Bcl-6 expression by CD4

    Meli, Alexandre P / Russell, Gabriel A / Swaminathan, Sharada / Weichselbaum, Laura / MacMahon, Clara A / Pernet, Erwan / Karo-Atar, Danielle / Rogers, Dakota / Rochette, Annie / Fontes, Ghislaine / Mandl, Judith N / Divangahi, Maziar / Klein, Ophir D / Gregorieff, Alex / Stäger, Simona / King, Irah L

    Mucosal immunology

    2023  Volume 16, Issue 6, Page(s) 801–816

    Abstract: Cluster of differentiation ( ... ...

    Abstract Cluster of differentiation (CD4
    MeSH term(s) Animals ; Interleukin-10 ; Parasitic Diseases ; Th2 Cells ; Nematoda
    Chemical Substances Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2023-09-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1016/j.mucimm.2023.08.004
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