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This study examined the in vitro immunological effects of co-administration of Thymosin-alpha-1 (T\u03b11) and polyanionic carbosilane dendrimers (PCDs) on peripheral blood mononuclear cells (PBMCs) during HCMV infection. The biocompatibility of PCDs was assessed via MTT and LDH assays. PBMCs were pre-treated with the co-administered compounds and then exposed to HCMV for 48 h. Morphological alterations in PBMCs were observed using optical microscopy and total dendritic cells (tDCs), myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with CD4+\/CD8+ T cells and regulatory T cells (Treg), and were characterized using multiparametric flow cytometry. The findings revealed that T\u03b11 + PCDs treatments increased DC activation and maturation. Furthermore, increased co-receptor expression, intracellular IFN\u03b3 production in T cells and elevated Treg functionality and reduced senescence were evident with T\u03b11 + G2-S24P treatment. Conversely, reduced co-receptor expression, intracellular cytokine production in T cells, lower functionality and higher senescence in Treg were observed with T\u03b11 + G2S16 treatment. In summary, T\u03b11 + PCDs treatments demonstrate synergistic effects during early HCMV infection, suggesting their use as an alternative therapeutic for preventing virus infection.<\/jats:p>","DOI":"10.3390\/ijms25041952","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T03:22:31Z","timestamp":1707189751000},"page":"1952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2271-6830","authenticated-orcid":false,"given":"Mar\u00eda de la Sierra","family":"Espinar-Buitrago","sequence":"first","affiliation":[{"name":"Section of Immunology, Immuno-Molecular Biology Laboratory (LIBM), University General Hospital Gregorio Mara\u00f1on (HGUGM), 28007 Madrid, Spain"},{"name":"Gregorio Mara\u00f1on Health Research Institute (IiSGM), 28009 Madrid, Spain"},{"name":"Center for Biomedical Research in Bioengineering, Biomaterials and Nanotechnology Network (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-7095","authenticated-orcid":false,"given":"Esmeralda","family":"Magro-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Section of Immunology, Immuno-Molecular Biology Laboratory (LIBM), University General Hospital Gregorio Mara\u00f1on (HGUGM), 28007 Madrid, Spain"},{"name":"Gregorio Mara\u00f1on Health Research Institute (IiSGM), 28009 Madrid, Spain"},{"name":"Center for Biomedical Research in Bioengineering, Biomaterials and Nanotechnology Network (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3011-9611","authenticated-orcid":false,"given":"Elena","family":"V\u00e1zquez-Alejo","sequence":"additional","affiliation":[{"name":"Section of Immunology, Immuno-Molecular Biology Laboratory (LIBM), University General Hospital Gregorio Mara\u00f1on (HGUGM), 28007 Madrid, Spain"},{"name":"Gregorio Mara\u00f1on Health Research Institute (IiSGM), 28009 Madrid, Spain"},{"name":"Center for Biomedical Research in Bioengineering, Biomaterials and Nanotechnology Network (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0813-4500","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"Mu\u00f1oz-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Section of Immunology, Immuno-Molecular Biology Laboratory (LIBM), University General Hospital Gregorio Mara\u00f1on (HGUGM), 28007 Madrid, Spain"},{"name":"Gregorio Mara\u00f1on Health Research Institute (IiSGM), 28009 Madrid, Spain"},{"name":"Center for Biomedical Research in Bioengineering, Biomaterials and Nanotechnology Network (CIBER-BBN), 28029 Madrid, Spain"},{"name":"HIV-HGM Biobank, University General Hospital Gregorio Mara\u00f1on (HGUGM), 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41579-021-00582-z","article-title":"Pathogenesis of human cytomegalovirus in the immunocompromised host","volume":"19","author":"Griffiths","year":"2021","journal-title":"Nat. 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