{
  "abstract": "Introduction: Glucocorticoids (GCs) such as dexamethasoneare widely used to treat allergies, autoimmune disorders, and chronic inflammatory conditions. However, their impact on antiviral immunity is complex and often contradictory. Clinically, dexamethasone can be beneficial in severe viral infections by suppressing excessive inflammation and limiting tissue injury. In contrast, during mild, early, or chronic infections, its immunosuppressive activity may delay viral clearance, promote viral replication or reactivation, and ultimately worsen disease outcomes. Reports describing both reduced and enhanced viral replication following GC treatment underscore the pleiotropic nature of GC action, yet the underlying mechanisms remain poorly understood.\n\nMethods: We investigated the effect of dexamethasone during persistent LCMV infection in wild-type (Mertk+/+) and MerTK-deficient (Mertk–/–) mice (20-25g body weight). Animals were infected with 2 × 104 PFU of the LCMV Docile strain intravenously and randomly assigned to two intervention arms, receiving either PBS or dexamethasone (2.5mg/kg, dose adjusted according to body weight) intraperitoneally every 48 hours.On day 8 post-infection, blood was collected prior to euthanasia, after which spleen and liver samples were harvested for flow-cytometric analysis. Viral titres were subsequently quantified in the spleen, liver, kidney, lung, and lymph nodes.\n\nResults: In Mertk+/+ mice, dexamethasone induced pronounced loss of CD8+ T cells and enhanced MerTK-dependent suppression of virus-specific CD8+ T cell responses, an effect largely absent in Mertk–/– animals. Functionally, dexamethasone substantially increases production of the anti-inflammatory cytokine IL-10 by macrophages and dendritic cells and elevates expression of the inhibitory checkpoint molecule PD-1 on LCMV-specific CD8+ T cells in Mertk+/+ mice. Moreover, expression of KLRG1, CD44, and CD127 on CD8+ T cells were substantially reduced, indicating impaired effector differentiation, whereas CD62L+ CD8+ T cells were upregulated, suggesting retention in a naïve or central-memory–like state. Together, these changes promoted functionally impaired CD8+ T cell phenotype, weakened LCMV-specific immunity, and facilitated viral dissemination across multiple organs examined. Genetic ablation of MerTK mitigated these immunosuppressive effects, resulting in significantly improved viral control.\n\nDiscussion: These findings demonstrate that the immunosuppressive effects of dexamethasone are critically dependent on the MerTK-mediated immunoregulatory axis. By identifying MerTK as a central node through which GCs reinforce inhibitory immune circuits, our study highlights MerTK as a potential target for future therapeutic intervention at the frontier of viral infections and inflammatory diseases. However, this therapeutic potential is currently supported solely by genetic loss-of-function evidence, and future studies employing pharmacological MerTK inhibition will be required to validate its efficacy and translational applicability.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp , ,",
    "Institute of Pathology, Section Immunopathology, Martin Luther University Halle-Wittenberg , ,",
    "Frazer Institute, The University of Queensland , , ,",
    "African Centre for Systematic Reviews and Knowledge Translation, Makerere University , ,",
    "Department of Cardiac Surgery, Uganda Heart Institute , ,",
    "The National Center for Radiation Research in Oncology , ,",
    "Medizinische Klinik und Poliklinik Zentrum für Innere Medizin , ,",
    "Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Health Sciences, Arabian Gulf University , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tom Adomati"
    },
    {
      "affs": [
        1
      ],
      "name": "Thamer A. Hamdan"
    },
    {
      "affs": [
        1
      ],
      "name": "Barbara Seliger"
    },
    {
      "affs": [
        2
      ],
      "name": "Vikas Duhan"
    },
    {
      "affs": [
        3
      ],
      "name": "Jacqueline E. Akite"
    },
    {
      "affs": [
        4
      ],
      "name": "Herbert Ariaka"
    },
    {
      "affs": [
        5
      ],
      "name": "Hilal Bhat"
    },
    {
      "affs": [
        6
      ],
      "name": "Murtaza Ali"
    },
    {
      "affs": [
        7
      ],
      "name": "Lamin B. Cham"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0b4ggwyfh9356.bib",
  "cited_by": 0,
  "doi": "10.3389/fcimb.2026.1961552",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730832/?tool=EBI",
  "id": "0b4ggwyfh9356",
  "issns": [
    "2235-2988"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13730832",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7223132718",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730832/pdf/?tool=EBI",
  "pmcid": "PMC13730832",
  "pmid": "42979660",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0b4ggwyfh9356.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:45Z",
      "native_id": "PMC:PMC13730832",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13730832"
    },
    {
      "first_seen": "2026-11-07T12:23:19Z",
      "native_id": "PMC13730832",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcimb.2026.1961552"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "MerTK mediates dexamethasone-induced suppression of antiviral CD8+ T cell immunity and exacerbates chronic LCMV infection",
  "title_text": "MerTK mediates dexamethasone-induced suppression of antiviral CD8+ T cell immunity and exacerbates chronic LCMV infection",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:23:19Z",
  "url": "https://research.draconitic.com/paper/0b4ggwyfh9356",
  "venue": "Frontiers in cellular and infection microbiology",
  "versions": []
}