{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:12:57Z","timestamp":1783941177206,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Dendritic cells (DC) play a crucial role in generating and maintaining antiviral immunity. While DC are implicated in the antiviral defense by inducing T cell responses, they can also become infected by Cytomegalovirus (CMV). CMV is not only highly species-specific but also specialized in evading immune protection, and this specialization is in part due to characteristic genes encoded by a given virus. Here, we investigated whether rat CMV can infect XCR1<jats:sup>+<\/jats:sup> DC and if infection of DC alters expression of cell surface markers and migration behavior. We demonstrate that wild-type RCMV and a mutant virus lacking the \u03b3-chemokine ligand <jats:italic>xcl1<\/jats:italic> (<jats:italic>\u0394vxcl1<\/jats:italic> RCMV<jats:italic>)<\/jats:italic> infect splenic rat DC <jats:italic>ex vivo<\/jats:italic> and identify viral assembly compartments. Replication-competent RCMV reduced XCR1 and MHCII surface expression. Further, gene expression of infected DC was analyzed by bulk RNA-sequencing (RNA-Seq). RCMV infection reverted a state of DC activation that was induced by DC cultivation. On the functional level, we observed impaired chemotactic activity of infected XCR1<jats:sup>+<\/jats:sup> DC compared to mock-treated cells. We therefore speculate that as a result of RCMV infection, DC exhibit diminished XCR1 expression and are thereby blocked from the lymphocyte crosstalk.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1192057","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:58:02Z","timestamp":1700740682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Rat cytomegalovirus efficiently replicates in dendritic cells and induces changes in their transcriptional profile"],"prefix":"10.3389","volume":"14","author":[{"given":"Julia Cecilia","family":"Madela-M\u00f6nchinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silver Anthony","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Wyler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Mischke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"M\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanda","family":"Jurani\u0107 Lisni\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Landthaler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Malyshkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Voigt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0966-842x(00)01830-8","article-title":"Viral mechanisms of immune evasion","volume":"8","author":"Alcami","year":"2000","journal-title":"Trends Microbiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ni724","article-title":"Infection of dendritic cells by murine cytomegalovirus induces functional paralysis","volume":"2","author":"Andrews","year":"2001","journal-title":"Nat Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408994102","article-title":"Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers","volume":"102","author":"Reeves","year":"2005","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-81-2-393","article-title":"Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus","volume":"81","author":"Riegler","year":"2000","journal-title":"J Gen Virol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.77.13.7563-7574.2003","article-title":"Susceptibility of immature and mature langerhans cell-type dendritic cells to infection and immunomodulation by human cytomegalovirus","volume":"77","author":"Hertel","year":"2003","journal-title":"J Virol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1743-422X-6-4","article-title":"Feeling manipulated: cytomegalovirus immune manipulation","volume":"6","author":"Miller-Kittrell","year":"2009","journal-title":"Virol J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nri2368","article-title":"The known unknowns of antigen processing and presentation","volume":"8","author":"Vyas","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abc7302","article-title":"Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells","volume":"6","author":"Yun","year":"2021","journal-title":"Sci Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.11.2.169","article-title":"Impaired function of antigen-presenting dendritic cells in patients with chronic hepatitis B: localization of HBV DNA and HBV RNA in blood DC by in situ hybridization","volume":"11","author":"Arima","year":"2003","journal-title":"Int J Mol Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.2204","article-title":"Dendritic cell susceptibility to hepatitis C virus genotype 1 infection","volume":"67","author":"Navas","year":"2002","journal-title":"J Med Virol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.15.7127-7136.2000","article-title":"Mature dendritic cells infected with herpes simplex virus type 1 exhibit inhibited T-cell stimulatory capacity","volume":"74","author":"Kruse","year":"2000","journal-title":"J Virol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3937","article-title":"Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells","volume":"95","author":"Hahn","year":"1998","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.13.6183-6192.2001","article-title":"Varicella-zoster virus infection of human dendritic cells and transmission to T cells: implications for virus dissemination in the host","volume":"75","author":"Abendroth","year":"2001","journal-title":"J Virol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.6.801","article-title":"Measles virus infects human dendritic cells and blocks their allostimulatory properties for CD4+ T cells","volume":"186","author":"Grosjean","year":"1997","journal-title":"J Exp Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1172\/JCI117399","article-title":"Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells","volume":"94","author":"Bhardwaj","year":"1994","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nri1960","article-title":"Dendritic-cell interactions with HIV: infection and viral dissemination","volume":"6","author":"Wu","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"7998","DOI":"10.1073\/pnas.88.18.7998","article-title":"Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures","volume":"88","author":"Langhoff","year":"1991","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01264-17","article-title":"Murine cytomegalovirus spreads by dendritic cell recirculation","volume":"8","author":"Farrell","year":"2017","journal-title":"mBio"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00540-19","article-title":"Murine cytomegalovirus spread depends on the infected myeloid cell type","volume":"93","author":"Farrell","year":"2019","journal-title":"J Virol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001333","article-title":"Murine cytomegalovirus disseminates independently of CX3CR1, CCL2 or its M131\/M129 chemokine homologue","volume":"100","author":"Farrell","year":"2019","journal-title":"J Gen Virol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/18038","article-title":"Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen","volume":"398","author":"Sigal","year":"1999","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00214","article-title":"Expression of XCR1 characterizes the Batf3-dependent lineage of dendritic cells capable of antigen cross-presentation","volume":"3","author":"Bachem","year":"2012","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00035","article-title":"Mouse Conventional Dendritic Cells Can be Universally Classified Based on the Mutually Exclusive Expression of XCR1 and SIRP\u03b1","volume":"6","author":"Gurka","year":"2015","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100348","article-title":"Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells","volume":"207","author":"Bachem","year":"2010","journal-title":"J Exp Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.2.1007","article-title":"Differential pattern recognition receptor expression but stereotyped responsiveness in rat spleen dendritic cell subsets","volume":"177","author":"Hubert","year":"2006","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.12.7485","article-title":"Rat plasmacytoid dendritic cells are an abundant subset of MHC class II+ CD4+CD11b-OX62- and type I IFN-producing cells that exhibit selective expression of Toll-like receptors 7 and 9 and strong responsiveness to CpG","volume":"172","author":"Hubert","year":"2004","journal-title":"J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2408","article-title":"Immature CD4- CD103+ Rat dendritic cells induce rapid caspase-independent apoptosis-like cell death in various tumor and nontumor cells and phagocytose their victims","volume":"175","author":"Trinite","year":"2005","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.5.2284","article-title":"Two phenotypically distinct subsets of spleen dendritic cells in rats exhibit different cytokine production and T cell stimulatory activity","volume":"169","author":"Voisine","year":"2002","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.8.4202","article-title":"A subset of cytolytic dendritic cells in rat","volume":"165","author":"Trinite","year":"2000","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1128\/JVI.02330-13","article-title":"Cytomegalovirus expresses the chemokine homologue vxcl1 capable of attracting XCR1+ CD4- dendritic cells","volume":"88","author":"Geyer","year":"2014","journal-title":"J Virol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.000109","article-title":"Rat cytomegalovirus (RCMV) English isolate and a newly identified Berlin isolate share similarities with but are separate as an anciently diverged clade from Mouse CMV and the Maastricht isolate of RCMV","volume":"96","author":"Geyer","year":"2015","journal-title":"J Gen Virol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02806","article-title":"Structure-Function Relationship of XCL1 Used for in vivo Targeting of Antigen Into XCR1+ Dendritic Cells","volume":"9","author":"Kroczek","year":"2018","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"jcs236190","DOI":"10.1242\/jcs.236190","article-title":"Rat cytomegalovirus-encoded gamma-chemokine vxcl1 is a highly adapted, species-specific agonist for rat XCR1-positive dendritic cells","volume":"133","author":"Bauer","year":"2019","journal-title":"J Cell Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu781","article-title":"QuasR: quantification and annotation of short reads in R","volume":"31","author":"Gaidatzis","year":"2015","journal-title":"Bioinformatics"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0463.2003.11107807.x","article-title":"Phenotype and function of rat dendritic cell subsets","volume":"111","author":"Yrlid","year":"2003","journal-title":"APMIS"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.08.027","article-title":"Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+ T cells","volume":"31","author":"Dorner","year":"2009","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100223","article-title":"The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells","volume":"207","author":"Crozat","year":"2010","journal-title":"J Exp Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.2.317","article-title":"Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures","volume":"185","author":"Winzler","year":"1997","journal-title":"J Exp Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.21.10018-10024.2000","article-title":"Incoming human cytomegalovirus pp65 (UL83) contained in apoptotic infected fibroblasts is cross-presented to CD8+ T cells by dendritic cells","volume":"74","author":"Arrode","year":"2000","journal-title":"J Virol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.11.013","article-title":"Dc infection promotes antiviral CTL priming: the \u2018Winkelried\u2019strategy","volume":"26","author":"Freigang","year":"2005","journal-title":"Trends Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.virol.2009.02.050","article-title":"Rat cytomegalovirus infection depletes MHC II in bone marrow derived dendritic cells","volume":"388","author":"Baca Jones","year":"2009","journal-title":"Virology"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.2978","article-title":"CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen","volume":"164","author":"Vremec","year":"2000","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199910)29:10<3245::AID-IMMU3245>3.0.CO;2-X","article-title":"Inhibition of dendritic cell maturation by herpes simplex virus","volume":"29","author":"Salio","year":"1999","journal-title":"Eur J Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.12.6762","article-title":"Vaccinia virus inhibits the maturation of human dendritic cells: A novel mechanism of immune evasion","volume":"163","author":"Engelmayer","year":"1999","journal-title":"J Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8720-8731.2004","article-title":"Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality","volume":"78","author":"Chang","year":"2004","journal-title":"J Virol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201243106","article-title":"Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation","volume":"43","author":"Manh","year":"2013","journal-title":"Eur J Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939414","article-title":"IL-12 and type I IFN response of neonatal myeloid DC to human CMV infection","volume":"39","author":"Renneson","year":"2009","journal-title":"Eur J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1192057\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:58:08Z","timestamp":1700740688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1192057\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":50,"alternative-id":["10.3389\/fimmu.2023.1192057"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1192057","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,23]]},"article-number":"1192057"}}