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  1. Article ; Online: Identification of macaque dendritic cell precursors in blood and tissue reveals their dysregulation in early SIV infection.

    Gardet, Margaux / Haigh, Oscar / Meurisse, Florian / Coindre, Sixtine / Dimant, Nastasia / Desjardins, Delphine / Bourgeois, Christine / Goujard, Cecile / Vaslin, Bruno / Relouzat, Francis / Le Grand, Roger / Lambotte, Olivier / Favier, Benoit

    Cell reports

    2024  Volume 43, Issue 4, Page(s) 113994

    Abstract: Distinct dendritic cell (DC) subsets play important roles in shaping immune responses. Circulating DC precursors (pre-DCs) are more susceptible to HIV infection in vitro, which may explain the inefficiency of immune responses against HIV. However, the ... ...

    Abstract Distinct dendritic cell (DC) subsets play important roles in shaping immune responses. Circulating DC precursors (pre-DCs) are more susceptible to HIV infection in vitro, which may explain the inefficiency of immune responses against HIV. However, the interplay between HIV and pre-DC is not defined in vivo. We identify human pre-DC equivalents in the cynomolgus macaque and then analyze their dynamics during simian immunodeficiency virus (SIV) infection to illustrate a sharp decrease of blood pre-DCs in early SIV infection and accumulation in lymph nodes (LNs), where they neglect to upregulate CD83/CD86 or MHC-II. Additionally, SIV infection attenuates the capacity of stimulated LN pre-DCs to produce IL-12p40. Analysis of HIV cohorts provides correlation between costimulatory molecule expression on pre-DCs and T cell activation in spontaneous HIV controllers. These findings pinpoint certain dynamics and functional changes of pre-DCs during SIV infection, providing a deeper understanding of immune dysregulation mechanisms elicited in people living with HIV.
    MeSH term(s) Animals ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Acquired Immunodeficiency Syndrome/blood ; Simian Acquired Immunodeficiency Syndrome/pathology ; Dendritic Cells/immunology ; Simian Immunodeficiency Virus/immunology ; Humans ; Lymph Nodes/immunology ; Lymph Nodes/pathology ; HIV Infections/immunology ; HIV Infections/virology ; HIV Infections/blood ; HIV Infections/pathology ; Macaca fascicularis ; Lymphocyte Activation/immunology
    Language English
    Publishing date 2024-03-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.113994
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Leukocyte Immunoglobulin-Like Receptors in Regulating the Immune Response in Infectious Diseases: A Window of Opportunity to Pathogen Persistence and a Sound Target in Therapeutics.

    Abdallah, Florence / Coindre, Sixtine / Gardet, Margaux / Meurisse, Florian / Naji, Abderrahim / Suganuma, Narufumi / Abi-Rached, Laurent / Lambotte, Olivier / Favier, Benoit

    Frontiers in immunology

    2021  Volume 12, Page(s) 717998

    Abstract: Immunoregulatory receptors are essential for orchestrating an immune response as well as appropriate inflammation in infectious and non-communicable diseases. Among them, leukocyte immunoglobulin-like receptors (LILRs) consist of activating and ... ...

    Abstract Immunoregulatory receptors are essential for orchestrating an immune response as well as appropriate inflammation in infectious and non-communicable diseases. Among them, leukocyte immunoglobulin-like receptors (LILRs) consist of activating and inhibitory receptors that play an important role in regulating immune responses modulating the course of disease progression. On the one hand, inhibitory LILRs constitute a safe-guard system that mitigates the inflammatory response, allowing a prompt return to immune homeostasis. On the other hand, because of their unique capacity to attenuate immune responses, pathogens use inhibitory LILRs to evade immune recognition, thus facilitating their persistence within the host. Conversely, the engagement of activating LILRs triggers immune responses and the production of inflammatory mediators to fight microbes. However, their heightened activation could lead to an exacerbated immune response and persistent inflammation with major consequences on disease outcome and autoimmune disorders. Here, we review the genetic organisation, structure and ligands of LILRs as well as their role in regulating the immune response and inflammation. We also discuss the LILR-based strategies that pathogens use to evade immune responses. A better understanding of the contribution of LILRs to host-pathogen interactions is essential to define appropriate treatments to counteract the severity and/or persistence of pathogens in acute and chronic infectious diseases lacking efficient treatments.
    MeSH term(s) Animals ; Autoimmunity ; Biomarkers ; Chromosome Mapping ; Communicable Diseases/etiology ; Communicable Diseases/metabolism ; Communicable Diseases/therapy ; Disease Management ; Disease Susceptibility/immunology ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunity ; Immunomodulation ; Leukocytes/immunology ; Leukocytes/metabolism ; Ligands ; Multigene Family ; Organ Specificity ; Protein Binding ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism
    Chemical Substances Biomarkers ; Ligands ; Receptors, Immunologic
    Language English
    Publishing date 2021-09-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.717998
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mass Cytometry Analysis Reveals Complex Cell-State Modifications of Blood Myeloid Cells During HIV Infection.

    Coindre, Sixtine / Tchitchek, Nicolas / Alaoui, Lamine / Vaslin, Bruno / Bourgeois, Christine / Goujard, Cecile / Lecuroux, Camille / Bruhns, Pierre / Le Grand, Roger / Beignon, Anne-Sophie / Lambotte, Olivier / Favier, Benoit

    Frontiers in immunology

    2019  Volume 10, Page(s) 2677

    Abstract: Dendritic cells (DC), which are involved in orchestrating early immune responses against pathogens, are dysregulated in their function by HIV infection. This dysregulation likely contributes to tip the balance toward viral persistence. Different DC ... ...

    Abstract Dendritic cells (DC), which are involved in orchestrating early immune responses against pathogens, are dysregulated in their function by HIV infection. This dysregulation likely contributes to tip the balance toward viral persistence. Different DC subpopulations, including classical (cDCs) and plasmacytoid (pDCs) dendritic cells, are subjected to concomitant inflammatory and immunoregulatory events during HIV infection, which hampers the precise characterization of their regulation through classical approaches. Here, we carried out mass cytometry analysis of blood samples from early HIV-infected patients that were longitudinally collected before and after 1 year of effective combination antiretroviral therapy (cART). Blood samples from HIV controller patients who naturally control the infection were also included. Our data revealed that plasma HIV RNA level was positively associated with a loss of cDC and pDC subpopulations that display high expression of LILR immunomodulatory receptors. Conversely, specific monocyte populations co-expressing high levels of HLA-I, 3 immunomodulatory receptors, CD64, LILRA2, and LILRB4, and the restriction factor CD317 (also known as BST2/Tetherin), were more abundant in early HIV-infection. Finally, our analysis revealed that the blood of HIV controller patients contained in a higher abundance a particular subtype of CD1c
    MeSH term(s) Adult ; Anti-HIV Agents/therapeutic use ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Female ; Flow Cytometry ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV-1/immunology ; Humans ; Male ; Middle Aged ; Monocytes/drug effects ; Monocytes/immunology ; Receptors, Immunologic/drug effects ; Receptors, Immunologic/immunology
    Chemical Substances Anti-HIV Agents ; Receptors, Immunologic
    Language English
    Publishing date 2019-11-22
    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.2019.02677
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Mass Cytometry Analysis Reveals the Landscape and Dynamics of CD32a

    Coindre, Sixtine / Tchitchek, Nicolas / Alaoui, Lamine / Vaslin, Bruno / Bourgeois, Christine / Goujard, Cecile / Avettand-Fenoel, Veronique / Lecuroux, Camille / Bruhns, Pierre / Le Grand, Roger / Beignon, Anne-Sophie / Lambotte, Olivier / Favier, Benoit

    Frontiers in immunology

    2018  Volume 9, Page(s) 1217

    Abstract: CD32a has been proposed as a specific marker of latently HIV-infected ... ...

    Abstract CD32a has been proposed as a specific marker of latently HIV-infected CD4
    MeSH term(s) Adult ; Antiretroviral Therapy, Highly Active ; Biomarkers ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/virology ; Case-Control Studies ; Female ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/metabolism ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Receptors, IgG/metabolism ; Viral Load ; Young Adult
    Chemical Substances Biomarkers ; Fc gamma receptor IIA ; Receptors, IgG
    Language English
    Publishing date 2018-06-04
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.01217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.

    Alaoui, Lamine / Palomino, Gustavo / Zurawski, Sandy / Zurawski, Gerard / Coindre, Sixtine / Dereuddre-Bosquet, Nathalie / Lecuroux, Camille / Goujard, Cecile / Vaslin, Bruno / Bourgeois, Christine / Roques, Pierre / Le Grand, Roger / Lambotte, Olivier / Favier, Benoit

    Cellular and molecular life sciences : CMLS

    2017  Volume 75, Issue 10, Page(s) 1871–1887

    Abstract: Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 ... ...

    Abstract Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.
    MeSH term(s) Adult ; Animals ; Cells, Cultured ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; HIV Infections/immunology ; HIV Infections/metabolism ; HIV-1 ; Histocompatibility Antigens Class I/metabolism ; Humans ; Macaca fascicularis ; Male ; Membrane Glycoproteins/metabolism ; Middle Aged ; Receptors, Immunologic/metabolism ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/metabolism ; Simian Immunodeficiency Virus ; Time Factors ; Young Adult
    Chemical Substances Histocompatibility Antigens Class I ; LILRB2 protein, human ; Membrane Glycoproteins ; Receptors, Immunologic
    Language English
    Publishing date 2017-11-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-017-2712-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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