{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:34:17Z","timestamp":1760150057823,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Agency for Science and Technology Promotion","award":["1554","1533","0966"],"award-info":[{"award-number":["1554","1533","0966"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Macrophages are exceptionally flexible cells. The presence of inflammatory cytokines such as IFN-\u03b3 and TNF-\u03b1 results in an M1 (CD68) activation, while cytokines such as IL-10 or TGF-\u03b2 induce the M2 (CD163) activation. Our aim was to study the behavior of peripheral cytokines involved in macrophage polarization and relate them with tissue findings to further comprehend the role of macrophages in EBV pediatric infection. We studied cytokine expression in tonsils and peripheral blood samples of children in different stages of infection. Peripheral cytokines were compared with macrophage polarization markers and viral protein expression in tonsils. Only IL-10 showed a negative correlation between compartments, exclusively in patients undergoing viral reactivation (R). Higher expressions of peripheral IL-1\u03b2, IL-23, and IL-12p40 in R children were observed. Lower expressions of local and peripheral TNF-\u03b1 in patients with broader expressions of latent and lytic viral proteins were demonstrated. In healthy carrier (HC) patients, IL-23 positively correlated with CD163, and IP-10 positively correlated with CD68. Our results indicated that EBV might modulate antigen expression in the presence of TNF-\u03b1 and influence peripheral cytokine expression differently in each stage of infection. Moreover, peripheral cytokines might have a particular role in macrophage polarization in HC.<\/jats:p>","DOI":"10.3390\/v15102105","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T08:10:19Z","timestamp":1697530219000},"page":"2105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["EBV Impact in Peripheral Macrophages\u2019 Polarization Cytokines in Pediatric Patients"],"prefix":"10.3390","volume":"15","author":[{"given":"Agustina","family":"Moyano","sequence":"first","affiliation":[{"name":"Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Molecular Biology Laboratory, Pathology Division, Ricardo Guti\u00e9rrez Children\u2019s Hospital, Buenos Aires 1425, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1210-3085","authenticated-orcid":false,"given":"Natalia","family":"Ferressini Gerpe","sequence":"additional","affiliation":[{"name":"Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Molecular Biology Laboratory, Pathology Division, Ricardo Guti\u00e9rrez Children\u2019s Hospital, Buenos Aires 1425, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Eugenia","family":"Amarillo","sequence":"additional","affiliation":[{"name":"Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Molecular Biology Laboratory, Pathology Division, Ricardo Guti\u00e9rrez Children\u2019s Hospital, Buenos Aires 1425, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"De Matteo","sequence":"additional","affiliation":[{"name":"Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Molecular Biology Laboratory, Pathology Division, Ricardo Guti\u00e9rrez Children\u2019s Hospital, Buenos Aires 1425, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Victoria","family":"Preciado","sequence":"additional","affiliation":[{"name":"Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Molecular Biology Laboratory, Pathology Division, Ricardo Guti\u00e9rrez Children\u2019s Hospital, Buenos Aires 1425, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-5878","authenticated-orcid":false,"given":"Maria Soledad","family":"Caldirola","sequence":"additional","affiliation":[{"name":"Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Molecular Biology Laboratory, Pathology Division, Ricardo Guti\u00e9rrez Children\u2019s Hospital, Buenos Aires 1425, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7355-3859","authenticated-orcid":false,"given":"Paola","family":"Chabay","sequence":"additional","affiliation":[{"name":"Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Molecular Biology Laboratory, Pathology Division, Ricardo Guti\u00e9rrez Children\u2019s Hospital, Buenos Aires 1425, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1007\/s12026-014-8496-1","article-title":"The Interplay between Epstein-Barr Virus and B Lymphocytes: Implications for Infection, Immunity, and Disease","volume":"58","author":"Hatton","year":"2014","journal-title":"Immunol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/s42003-021-02501-7","article-title":"Phase Separation of Epstein-Barr Virus EBNA2 Protein Reorganizes Chromatin Topology for Epigenetic Regulation","volume":"4","author":"Yang","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Arvin, A., Campadelli-Fiume, G., Mocarski, E., Moore, P.S., Roizman, B., Whitley, R., and Yamanishi, K. (2007). Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis, Cambridge University Press.","DOI":"10.1017\/CBO9780511545313"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.exphem.2005.11.008","article-title":"Epstein-Barr Virus, Cytokines, and Inflammation: A Cocktail for the Pathogenesis of Hodgkin\u2019s Lymphoma?","volume":"34","author":"Khan","year":"2006","journal-title":"Exp. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"713","DOI":"10.3389\/fonc.2019.00713","article-title":"The Global Landscape of EBV-Associated Tumors","volume":"9","author":"Rickinson","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1002\/ijc.27858","article-title":"EBV Primary Infection in Childhood and Its Relation to B-Cell Lymphoma Development: A Mini-Review from a Developing Region","volume":"133","author":"Chabay","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jcv.2018.03.001","article-title":"Primary Epstein-Barr Virus Infection","volume":"102","author":"Dunmire","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jayasooriya, S., de Silva, T.I., Njie-jobe, J., Sanyang, C., Leese, A.M., Bell, A.I., McAulay, K.A., Yanchun, P., Long, H.M., and Dong, T. (2015). Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004746"},{"key":"ref_9","first-page":"325","article-title":"T-Cell Responses to EBV","volume":"391","author":"Hislop","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1182\/blood-2014-01-553024","article-title":"Role for Early-Differentiated Natural Killer Cells in Infectious Mononucleosis","volume":"124","author":"Azzi","year":"2014","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.celrep.2013.11.041","article-title":"Human Natural Killer Cells Prevent Infectious Mononucleosis Features by Targeting Lytic Epstein-Barr Virus Infection","volume":"5","author":"Chijioke","year":"2013","journal-title":"Cell Rep."},{"key":"ref_12","first-page":"265","article-title":"Innate Immune Recognition of EBV","volume":"391","author":"Rowe","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s00430-018-0553-2","article-title":"The Interplay between Local Immune Response and Epstein-Barr Virus-Infected Tonsillar Cells Could Lead to Viral Infection Control","volume":"207","author":"Vistarop","year":"2018","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e0143421","DOI":"10.1128\/JVI.01434-21","article-title":"M1 Macrophage Polarization Prevails in Epstein-Barr Virus-Infected Children in an Immunoregulatory Environment","volume":"96","author":"Moyano","year":"2022","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/imr.12223","article-title":"Macrophage Heterogeneity in Tissues: Phenotypic Diversity and Functions","volume":"262","author":"Gordon","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 Paradigm of Macrophage Activation: Time for Reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000Prime Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.3389\/fimmu.2018.01930","article-title":"Chemokine-Induced Macrophage Polarization in Inflammatory Conditions","volume":"9","author":"Ruytinx","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage Polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage Plasticity, Polarization, and Function in Health and Disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1100\/2011\/213962","article-title":"Macrophage Polarization in Health and Disease","volume":"11","author":"Cassetta","year":"2011","journal-title":"Sci. World J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100776","DOI":"10.1016\/j.esmoop.2022.100776","article-title":"Macrophage and Monocyte Subsets as New Therapeutic Targets in Cancer Immunotherapy","volume":"8","author":"Fendl","year":"2023","journal-title":"ESMO Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.ejca.2006.01.003","article-title":"Tumour-Associated Macrophages Are a Distinct M2 Polarised Population Promoting Tumour Progression: Potential Targets of Anti-Cancer Therapy","volume":"42","author":"Sica","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"740588","DOI":"10.3389\/fimmu.2022.740588","article-title":"FOXP3\/HAT1 Axis Controls Treg Infiltration in the Tumor Microenvironment by Inducing CCR4 Expression in Breast Cancer","volume":"13","author":"Sarkar","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1182\/blood-2017-03-770719","article-title":"Topological Analysis Reveals a PD-L1-Associated Microenvironmental Niche for Reed-Sternberg Cells in Hodgkin Lymphoma","volume":"130","author":"Carey","year":"2017","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"940910","DOI":"10.3389\/fimmu.2022.940910","article-title":"PD-L1 Is Upregulated in CD163+ Tonsillar Macrophages from Children Undergoing EBV Primary Infection","volume":"13","author":"Moyano","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101652","DOI":"10.1016\/j.smim.2022.101652","article-title":"Natural Killer Cell Responses to Human Oncogenic \u03b3-Herpesvirus Infections","volume":"60","year":"2022","journal-title":"Semin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijid.2020.01.044","article-title":"Distinctive EBV Infection Characteristics in Children from a Developing Country","volume":"93","author":"Vistarop","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-319-54090-0_1","article-title":"Evolutionary Aspects of Macrophages Polarization","volume":"62","author":"Edholm","year":"2017","journal-title":"Results Probl. Cell Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.3390\/cancers6031670","article-title":"Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment","volume":"6","author":"Chanmee","year":"2014","journal-title":"Cancers"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.1158\/1078-0432.CCR-12-0129","article-title":"Tumor-Associated Macrophages in Pediatric Classical Hodgkin Lymphoma: Association with Epstein-Barr Virus, Lymphocyte Subsets, and Prognostic Impact","volume":"18","author":"Barros","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12687","DOI":"10.1038\/s41598-019-49015-1","article-title":"M1-like Macrophage Polarization Prevails in Young Children with Classic Hodgkin Lymphoma from Argentina","volume":"9","author":"Jimenez","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1182\/blood-2018-08-870915","article-title":"Serum Levels of TARC, MDC, IL-10, and Soluble CD163 in Hodgkin Lymphoma: A SWOG S0816 Correlative Study","volume":"133","author":"Hsi","year":"2019","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dunmire, S.K., Odumade, O.A., Porter, J.L., Reyes-Genere, J., Schmeling, D.O., Bilgic, H., Fan, D., Baechler, E.C., Balfour, H.H., and Hogquist, K.A. (2014). Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085422"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Budiningsih, I., Dachlan, Y.P., Hadi, U., and Middeldorp, J.M. (2021). Quantitative Cytokine Level of TNF-\u03b1, IFN-\u03b3, IL-10, TGF-\u03b2 and Circulating Epstein-Barr Virus DNA Load in Individuals with Acute Malaria due to P. falciparum or P. vivax or Double Infection in a Malaria Endemic Region in Indonesia. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0261923"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2105\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:08:26Z","timestamp":1760130506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,17]]},"references-count":34,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["v15102105"],"URL":"https:\/\/doi.org\/10.3390\/v15102105","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2023,10,17]]}}}