{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:50:00Z","timestamp":1782190200733,"version":"3.54.5"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"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. Vet. Sci."],"abstract":"<jats:p>\n                    <jats:italic>Varicellovirus bovinealpha1<\/jats:italic>\n                    (BoAHV-1) is an important cause of reproductive failure in cattle and can induce abortion following transplacental infection during late gestation. However, immune-associated responses at the conceptus (placenta and fetus) remain incompletely understood. This study aimed to characterize maternal and fetal immune-associated responses to BoAHV-1 vertical infection by evaluating the expression of endosomal Toll-like receptors (\n                    <jats:italic>TLR3<\/jats:italic>\n                    ,\n                    <jats:italic>TLR7<\/jats:italic>\n                    and\n                    <jats:italic>TLR9<\/jats:italic>\n                    ), cytokines, and the antimicrobial peptide\n                    <jats:italic>BMAP28<\/jats:italic>\n                    , together with the distribution of immune-cell markers in placental and fetal tissues. Pregnant dams (infected,\n                    <jats:italic>n\u202f=<\/jats:italic>\n                    \u202f7; controls,\n                    <jats:italic>n\u202f=<\/jats:italic>\n                    \u202f4) were experimentally infected with BoAHV-1 during late gestation and euthanized at 15 days post-infection (dpi). Peripheral blood leukocytes (PBLs) were collected at 3 and 10 dpi, and placental and fetal tissue samples were collected during necropsy. Relative mRNA expression of innate immune genes was assessed by RT-qPCR, while immune-cell markers were characterized by immunohistochemistry. Maternal tissues, including PBLs and placental caruncles, showed reduced expression of\n                    <jats:italic>TLR9<\/jats:italic>\n                    and\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    . Fetal lungs showed increased expression of endosomal TLRs,\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>IL-12<\/jats:italic>\n                    and\n                    <jats:italic>BMAP28<\/jats:italic>\n                    , accompanied by increase of CD3\n                    <jats:sup>+<\/jats:sup>\n                    cells and iNOS-associated cells. The fetal spleen showed specific changes in gene expression, whereas the fetal liver presented a distinct transcriptional pattern with increased TLR expression and reduced cytokine transcript levels. Overall, BoAHV-1 transplacental late infection was associated with distinct patterns of immune-related gene expression and immune-cell marker distribution across maternal, placental and fetal tissues, providing an integrated view of immune-associated responses at day 15 post-infection.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2026.1845115","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:30:13Z","timestamp":1782189013000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Compartment-specific immune responses to BoAHV-1 transplacental infection in late gestation"],"prefix":"10.3389","volume":"13","author":[{"given":"Felipe","family":"Cheuquep\u00e1n","sequence":"first","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["Buenos Aires, Argentina"]},{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMDP)","place":["Mar del Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Agull\u00f3-Ros","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda y Anatom\u00eda Patol\u00f3gica Comparadas y Toxicolog\u00eda, Grupo de Investigaci\u00f3n GISAZ, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de C\u00f3rdoba","place":["C\u00f3rdoba, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda A.","family":"Risalde","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda y Anatom\u00eda Patol\u00f3gica Comparadas y Toxicolog\u00eda, Grupo de Investigaci\u00f3n GISAZ, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de C\u00f3rdoba","place":["C\u00f3rdoba, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes M.","family":"Buruc\u00faa","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["Buenos Aires, Argentina"]},{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMDP)","place":["Mar del Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvina","family":"Quintana","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones de Producci\u00f3n, Sanidad y Ambiente (IIPROSAM), FCEyN, UNMDP-CONICET","place":["Mar del Plata, Argentina"]},{"name":"Instituto de Biolog\u00eda Molecular Aplicada","place":["Mar del Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pl\u00e1","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["Buenos Aires, Argentina"]},{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMDP)","place":["Mar del Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Veterinarias de Tandil (CIVETAN) - CONICET, Facultad de Ciencias Veterinarias, UNCPBA","place":["Tandil, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Valeria","family":"Scioli","sequence":"additional","affiliation":[{"name":"Instituto de Innovaci\u00f3n para la Producci\u00f3n Agropecuaria y el Desarrollo Sostenible (IPADS, INTA-CONICET)","place":["Balcarce, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germ\u00e1n J.","family":"Cant\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Innovaci\u00f3n para la Producci\u00f3n Agropecuaria y el Desarrollo Sostenible (IPADS, INTA-CONICET)","place":["Balcarce, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dadin P.","family":"Moore","sequence":"additional","affiliation":[{"name":"Instituto de Innovaci\u00f3n para la Producci\u00f3n Agropecuaria y el Desarrollo Sostenible (IPADS, INTA-CONICET)","place":["Balcarce, Argentina"]},{"name":"Facultad de Ciencias Agrarias, UNMDP","place":["Balcarce, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselmo C.","family":"Ode\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Agrarias, UNMDP","place":["Balcarce, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia S.","family":"Marin","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["Buenos Aires, Argentina"]},{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMDP)","place":["Mar del Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora L.","family":"Morrell","sequence":"additional","affiliation":[{"name":"Instituto de Innovaci\u00f3n para la Producci\u00f3n Agropecuaria y el Desarrollo Sostenible (IPADS, INTA-CONICET)","place":["Balcarce, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v15010234","article-title":"The bovine herpesvirus 1 latency-reactivation cycle, a chronic problem in the cattle industry","volume":"15","author":"Ostler","year":"2023","journal-title":"Viruses"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1051\/vetres:2006059","article-title":"Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis","volume":"38","author":"Muylkens","year":"2007","journal-title":"Vet Res"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.prevetmed.2017.01.005","article-title":"Prevention of abortion in cattle following vaccination against bovine herpesvirus 1: a meta-analysis","volume":"138","author":"Newcomer","year":"2017","journal-title":"Prev Vet Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/1297-9716-44-91","article-title":"Development of maternal and foetal immune responses in cattle following experimental challenge with Neospora caninum at day 210 of gestation","volume":"44","author":"Bartley","year":"2013","journal-title":"Vet Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.cvfa.2007.11.001","article-title":"Neonatal immune development in the calf and its impact on vaccine response","volume":"24","author":"Chase","year":"2008","journal-title":"Vet Clin N Am Food Anim Pract"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1093\/biolre\/ioac107","article-title":"The ruminant placental trophoblast binucleate cell: an evolutionary breakthrough","volume":"107","author":"Wooding","year":"2022","journal-title":"Biol Reprod"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.virusres.2012.05.018","article-title":"Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus","volume":"167","author":"Smirnova","year":"2012","journal-title":"Virus Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat Immunol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1093\/jleuko\/qiae112","article-title":"The role of cathelicidins in neutrophil biology","volume":"116","author":"Yoon","year":"2024","journal-title":"J Leukoc Biol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.rvsc.2013.11.015","article-title":"Toll-like receptor activation and expression in bovine alpha-herpesvirus infections","volume":"96","author":"Marin","year":"","journal-title":"Res Vet Sci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.rvsc.2014.06.014","article-title":"Toll-like receptor expression in the nervous system of bovine alpha- herpesvirus-infected calves","volume":"97","author":"Marin","year":"","journal-title":"Res Vet Sci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.rvsc.2016.02.002","article-title":"Involvement of toll-like receptors 3 and 7\/8 in the neuropathogenesis of bovine herpesvirus type 1 and 5","volume":"107","author":"Rensetti","year":"2016","journal-title":"Res Vet Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.rvsc.2016.01.002","article-title":"Bovine alpha-herpesviruses distribution and toll-like receptors expression in the respiratory system of experimentally infected calves","volume":"105","author":"Marin","year":"2016","journal-title":"Res Vet Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/j.1600-0897.2010.00848.x","article-title":"Toll-like receptors at the maternal-fetal interface in normal pregnancy and pregnancy disorders","volume":"63","author":"Koga","year":"2010","journal-title":"Am J Reprod Immunol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1111\/rda.13983","article-title":"Macrophages in bovine term placenta: an ultrastructural and molecular study","volume":"56","author":"Hooshmandabbasi","year":"2021","journal-title":"Reprod Domest Anim"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/vaccines11040785","article-title":"The cell-mediated immune response against bovine alphaherpesvirus 1 (BoHV-1) infection and vaccination","volume":"11","author":"Righi","year":"2023","journal-title":"Vaccine"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e03814","DOI":"10.1128\/spectrum.03814-22","article-title":"Several alphaherpesviruses interact similarly with the NF-\u03baB pathway, suppress NF-\u03baB-dependent gene expression","volume":"10","author":"Romero","year":"2023","journal-title":"Microbiol Spectrum"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"839585","DOI":"10.3389\/fmicb.2022.839585","article-title":"Modulation of macrophage polarization by viruses: turning off\/on host antiviral responses","volume":"13","author":"Yu","year":"2022","journal-title":"Front Microbiol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12931-018-0777-0","article-title":"Human alveolar macrophages predominately express combined classical M1 and M2 surface markers in steady state","volume":"19","author":"Mitsi","year":"2018","journal-title":"Respir Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e13213","DOI":"10.1371\/journal.pone.0013213","article-title":"Differentiation of the endometrial macrophage during pregnancy in the cow","volume":"5","author":"Oliveira","year":"2010","journal-title":"PLoS One"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"109912","DOI":"10.1016\/j.vetmic.2023.109912","article-title":"Transplacental infection by bovine alphaherpesvirus type 1 induces protein expression of COX-2, iNOS and inflammatory cytokines in fetal lungs and placentas","volume":"287","author":"Buruc\u00faa","year":"2023","journal-title":"Vet Microbiol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.jcpa.2007.04.022","article-title":"Microscopical lesions and antigen distribution in bovine fetal tissues and placentae following experimental infection with bovine Herpesvirus-1 during pregnancy","volume":"137","author":"Rodger","year":"2007","journal-title":"J Comp Pathol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1590\/1678-5150-pvb-5668","article-title":"Current trends in bovine abortion in Argentina","volume":"39","author":"Morrell","year":"2019","journal-title":"Pesquisa Vet. Brasileira"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.vetimm.2004.01.003","article-title":"Quantitative analysis of pro-inflammatory cytokine mRNA expression in Theileria annulata-infected cell lines derived from resistant and susceptible cattle","volume":"99","author":"McGuire","year":"2004","journal-title":"Vet Immunol Immunopathol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1297-9716-44-20","article-title":"Pathogenic mechanisms implicated in the intravascular coagulation in the lungs of BVDV-infected calves challenged with BHV-1","volume":"44","author":"Risalde","year":"2013","journal-title":"Vet Res"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.molimm.2019.04.022","article-title":"Modulation of cathelicidins, IFN\u03b2 and TNF\u03b1 by bovine alpha-herpesviruses is dependent on the stage of the infectious cycle","volume":"111","author":"Buruc\u00faa","year":"2019","journal-title":"Mol Immunol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e11892","DOI":"10.7717\/peerj.11892","article-title":"Influenza a virus infects pulmonary microvascular endothelial cells leading to microvascular leakage and release of pro-inflammatory cytokines","volume":"9","author":"Han","year":"2021","journal-title":"PeerJ"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e1006757","DOI":"10.1371\/journal.ppat.1006757","article-title":"H1N1 influenza virus infection results in adverse pregnancy outcomes by disrupting tissue-specific hormonal regulation","volume":"13","author":"Littauer","year":"2017","journal-title":"PLoS Pathog"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1177\/1040638712448187","article-title":"Bovine herpesvirus 1 abortion: current prevalence in the United Kingdom and evidence of hematogenous spread within the fetus in natural cases","volume":"24","author":"Crook","year":"2012","journal-title":"J Vet Diagn Invest"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"353","DOI":"10.3177\/jnsv.56.353","article-title":"Effects of vitamin E on reproductive protection in pregnant mice infected with pseudorabies virus (PRV) via regulating expression of toll-like receptors (TLRs) and cytokine balance","volume":"56","author":"Wu","year":"2010","journal-title":"J Nutr Sci Vitaminol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13567-015-0290-0","article-title":"Systemic and local immune responses in sheep after Neospora caninum experimental infection at early, mid and late gestation","volume":"47","author":"Arranz-Sol\u00eds","year":"2016","journal-title":"Vet Res"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"109942","DOI":"10.1016\/j.vetimm.2019.109942","article-title":"Characterization of CD79\u03b1cy+ cells in placentas from ruminants","volume":"217","author":"Cant\u00f3n","year":"2019","journal-title":"Vet Immunol Immunopathol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2015.00263","article-title":"Much more than M1 and M2 macrophages, there are also CD169+ and TCR+ macrophages","volume":"6","author":"Ch\u00e1vez-Gal\u00e1n","year":"2015","journal-title":"Front Immunol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0156004","article-title":"East coast fever caused by Theileria parva is characterized by macrophage activation associated with vasculitis and respiratory failure","volume":"11","author":"Fry","year":"2016","journal-title":"PLoS One"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1369\/jhc.5A6871.2006","article-title":"AM-3K, an anti-macrophage antibody, recognizes CD163, a molecule associated with an anti-inflammatory macrophage phenotype","volume":"54","author":"Komohara","year":"2006","journal-title":"J Histochem Cytochem"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"14974","DOI":"10.1038\/s41598-024-65868-7","article-title":"Phenotypic characterisation of bovine alveolar macrophages reveals two major subsets with differential expression of CD163","volume":"14","author":"Randall","year":"2024","journal-title":"Sci Rep"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1128\/IAI.01090-09","article-title":"Broad-spectrum activity against bacterial mastitis pathogens and activation of mammary epithelial cells support a protective role of neutrophil cathelicidins in bovine mastitis","volume":"78","author":"Tomasinsig","year":"2010","journal-title":"Infect Immun"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1297-9716-45-10","article-title":"Neospora caninum infection during early pregnancy in cattle: how the isolate influences infection dynamics, clinical outcome and peripheral and local immune responses","volume":"45","author":"Regidor-Cerrillo","year":"2014","journal-title":"Vet Res"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1017\/S146625230700134X","article-title":"A review of the biology of bovine herpesvirus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex and development of improved vaccines","volume":"8","author":"Jones","year":"1996","journal-title":"Animal Health Research Reviews"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1845115\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:30:17Z","timestamp":1782189017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1845115\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":41,"alternative-id":["10.3389\/fvets.2026.1845115"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2026.1845115","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"article-number":"1845115"}}