{
    "abstract": "Aging alters immune function in women and can lead increased risk of infections, particularly in the female reproductive tract (FRT).\nTo determine how aging affects innate immune responses in the cervical stroma of the FRT, we isolated endocervical (CX) and ectocervical (ECX) stromal fibroblasts and determine if their expression of multiple pattern recognition receptors (PRRs) and responses to viral stimulation varied with menopause and age.\nConstitutive expression of most PRRs did not vary with age or menopausal status in either cell type. However, the expression of TLR7, MDA5, and NOD2 by ECX stromal fibroblasts significantly increased in post-menopausal women, while the expression of NOD1 by CX stromal fibroblast also significantly increased in post-menopausal women. When stratified by age, the expression of TLR6 by CX stromal fibroblasts, and MDA5 and NOD2 by ECX stromal fibroblasts increased significantly with increasing age. Stimulation with the dsRNA viral mimic HMW poly (I:C), a ligand for MDA5, resulted in significantly increased expression of the Type I interferons (IFN) IFN\u03b2 and IFN\u03b5, the Type III interferon IFN\u03bb1, and interferon-stimulated genes (ISGs) MxA, OAS2, and ISG15 in both cell populations. However, upregulation of IFN\u03b2, IFN\u03bb1, MxA, OAS2, and ISG15 in response to poly (I:C) significantly declined with increasing post-menopausal age in ECX stromal fibroblasts. There was no effect of age or menopause on either IFN or ISG expression in CX stromal fibroblasts.\nOverall, these studies demonstrate that ECX and CX fibroblasts are phenotypically distinct populations and that increasing post-menopausal age reduces IFN and ISG upregulation in ECX stromal fibroblasts in response to viral stimulation, potentially leading to decreased protection against incoming viral pathogens in older post-menopausal women.",
    "authors": [
        {
            "affiliation": "Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.",
            "firstname": "Mickey V",
            "initials": "MV",
            "lastname": "Patel"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.",
            "firstname": "Zheng",
            "initials": "Z",
            "lastname": "Shen"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.",
            "firstname": "Daniel C",
            "initials": "DC",
            "lastname": "Hopkins"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.",
            "firstname": "Fiona D",
            "initials": "FD",
            "lastname": "Barr"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.",
            "firstname": "Charles R",
            "initials": "CR",
            "lastname": "Wira"
        }
    ],
    "conclusions": "Overall, these studies demonstrate that ECX and CX fibroblasts are phenotypically distinct populations and that increasing post-menopausal age reduces IFN and ISG upregulation in ECX stromal fibroblasts in response to viral stimulation, potentially leading to decreased protection against incoming viral pathogens in older post-menopausal women.",
    "copyrights": "\u00a9 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
    "doi": "10.1111/aji.70031",
    "journal": "American journal of reproductive immunology (New York, N.Y. : 1989)",
    "keywords": [
        "TLRs",
        "aging",
        "cytokines",
        "fibroblasts",
        "innate immunity",
        "interferon\u2010stimulated genes"
    ],
    "methods": null,
    "publication_date": "2025-01-09",
    "pubmed_id": "39777771",
    "results": "Constitutive expression of most PRRs did not vary with age or menopausal status in either cell type. However, the expression of TLR7, MDA5, and NOD2 by ECX stromal fibroblasts significantly increased in post-menopausal women, while the expression of NOD1 by CX stromal fibroblast also significantly increased in post-menopausal women. When stratified by age, the expression of TLR6 by CX stromal fibroblasts, and MDA5 and NOD2 by ECX stromal fibroblasts increased significantly with increasing age. Stimulation with the dsRNA viral mimic HMW poly (I:C), a ligand for MDA5, resulted in significantly increased expression of the Type I interferons (IFN) IFN\u03b2 and IFN\u03b5, the Type III interferon IFN\u03bb1, and interferon-stimulated genes (ISGs) MxA, OAS2, and ISG15 in both cell populations. However, upregulation of IFN\u03b2, IFN\u03bb1, MxA, OAS2, and ISG15 in response to poly (I:C) significantly declined with increasing post-menopausal age in ECX stromal fibroblasts. There was no effect of age or menopause on either IFN or ISG expression in CX stromal fibroblasts.",
    "title": "Aging Selectively Alters PRR and ISG Expression in Endo- and Ecto-Cervical Stromal Fibroblasts From the Human Female Reproductive Tract.",
    "xml": "<Element 'PubmedArticle' at 0x788503bb8d10>"
}