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  1. Article ; Online: Cytokines and chemokines: The vital role they play in herpes simplex virus mucosal immunology.

    Smith, Jacinta B / Herbert, Jason J / Truong, Naomi R / Cunningham, Anthony L

    Frontiers in immunology

    2022  Volume 13, Page(s) 936235

    Abstract: Herpes simplex viruses (HSV) types 1 and 2 are ubiquitous infections in humans. They cause orofacial and genital herpes with occasional severe complications. HSV2 also predisposes individuals to infection with HIV. There is currently no vaccine or ... ...

    Abstract Herpes simplex viruses (HSV) types 1 and 2 are ubiquitous infections in humans. They cause orofacial and genital herpes with occasional severe complications. HSV2 also predisposes individuals to infection with HIV. There is currently no vaccine or immunotherapy for these diseases. Understanding the immunopathogenesis of HSV infections is essential to progress towards these goals. Both HSV viruses result in initial infections in two major sites - in the skin or mucosa, either after initial infection or recurrence, and in the dorsal root or trigeminal ganglia where the viruses establish latency. HSV1 can also cause recurrent infection in the eye. At all of these sites immune cells respond to control infection. T cells and resident dendritic cells (DCs) in the skin/mucosa and around reactivating neurones in the ganglia, as well as keratinocytes in the skin and mucosa, are major sources of cytokines and chemokines. Cytokines such as the Type I and II interferons synergise in their local antiviral effects. Chemokines such as CCL2, 3 and 4 are found in lesion vesicle fluid, but their exact role in determining the interactions between epidermal and dermal DCs and with resident memory and infiltrating CD4 and CD8 T cells in the skin/mucosa is unclear. Even less is known about these mechanisms in the ganglia. Here we review the data on known sources and actions of these cytokines and chemokines at cellular and tissue level and indicate their potential for preventative and therapeutic interventions.
    MeSH term(s) Antiviral Agents ; Chemokines ; Cytokines ; Herpes Simplex ; Herpesvirus 1, Human ; Humans ; Interferons ; Mucous Membrane
    Chemical Substances Antiviral Agents ; Chemokines ; Cytokines ; Interferons (9008-11-1)
    Language English
    Publishing date 2022-09-23
    Publishing country Switzerland
    Document type Journal Article ; Review ; 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.2022.936235
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways.

    Bertram, Kirstie M / Truong, Naomi R / Smith, Jacinta B / Kim, Min / Sandgren, Kerrie J / Feng, Konrad L / Herbert, Jason J / Rana, Hafsa / Danastas, Kevin / Miranda-Saksena, Monica / Rhodes, Jake W / Patrick, Ellis / Cohen, Ralph C / Lim, Jake / Merten, Steven L / Harman, Andrew N / Cunningham, Anthony L

    PLoS pathogens

    2021  Volume 17, Issue 4, Page(s) e1009536

    Abstract: Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is ...

    Abstract Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.
    MeSH term(s) Adolescent ; Animals ; Cells, Cultured ; Child ; Child, Preschool ; Chlorocebus aethiops ; Epidermis/pathology ; Epidermis/virology ; HaCaT Cells ; HeLa Cells ; Herpes Simplex/pathology ; Herpes Simplex/virology ; Herpesvirus 1, Human/physiology ; Humans ; Infant ; Langerhans Cells/virology ; Signal Transduction/physiology ; Vero Cells ; Virus Internalization
    Language English
    Publishing date 2021-04-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1009536
    Database MEDical Literature Analysis and Retrieval System OnLINE

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