{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:15Z","timestamp":1760144955380,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["GR-2016-02361497"],"award-info":[{"award-number":["GR-2016-02361497"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Linea 1-Ricerca Corrente","award":["GR-2016-02361497"],"award-info":[{"award-number":["GR-2016-02361497"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Cystic echinococcosis (CE) cysts may persist for decades because of immune modulation mechanisms. Here, we characterize the cysts and the blood immune responses in patients with CE. Methods: We enrolled 61 patients with CE and 19 control subjects. We received tissue samples from seven patients with CE and a control subject requiring liver cystectomy. The immunohistochemistry evaluation of the immune cell subtypes and cytokines in the pericysts and surrounding liver and the antigen B (AgB)-specific response analysis of whole blood were performed. Results: In CE, the pericyst and the surrounding liver parenchyma showed aggregates of CD3+ T lymphocytes, mainly CD4+. B lymphocyte aggregates were present in the liver tissue. Monocytes\/granulocytes were rarely observed. Th2 cytokine expression was scarce, whereas IFN-\u03b3 expression was present in the CE tissues. The control subject did not show an inflammatory infiltrate. The IL-4-specific response to AgB was increased in the patients with CE compared to the control, and this result was confirmed in a larger cohort (p = 0.003), whereas the IFN-\u03b3-response was similar between the two groups (p = 0.5570). Conclusion: In patients with CE, CD4+ lymphocytes infiltrate the pericyst and the surrounding liver tissue with a low IL-4\/IL-13 expression level and a moderate IFN-\u03b3 expression level; moreover, an IL-4 parasite-specific response is detected in the periphery. These results support adventitia involvement in CE immunopathogenesis.<\/jats:p>","DOI":"10.3390\/pathogens13060477","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T03:49:28Z","timestamp":1717559368000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Local and Peripheral Immune Responses in Patients with Cystic Echinococcosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Linda","family":"Petrone","sequence":"first","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases (INMI) \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-8934","authenticated-orcid":false,"given":"Saeid","family":"Najafi-Fard","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases (INMI) \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8752-2415","authenticated-orcid":false,"given":"Laura","family":"Falasca","sequence":"additional","affiliation":[{"name":"Laboratory of Electron Microscopy, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Settimia","family":"Sbarra","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases (INMI) \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Teggi","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases, Sant\u2019Andrea Hospital University of Rome \u201cSapienza\u201d, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5606-8712","authenticated-orcid":false,"given":"Emanuele","family":"Nicastri","sequence":"additional","affiliation":[{"name":"Clinical Division of Infectious Diseases, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia Rosalba","family":"Grillo","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Unit, San Camillo-Forlanini Hospital, 00152 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirco","family":"Burocchi","sequence":"additional","affiliation":[{"name":"Division of General Surgery and Liver Transplantation, San Camillo-Forlanini Hospital, 00152 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe Maria","family":"Ettorre","sequence":"additional","affiliation":[{"name":"Division of General Surgery and Liver Transplantation, San Camillo-Forlanini Hospital, 00152 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Ludovisi","sequence":"additional","affiliation":[{"name":"Foodborne and Neglected Parasitoses Unit, Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Colombo","sequence":"additional","affiliation":[{"name":"Pathology Unit, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franca","family":"Del Nonno","sequence":"additional","affiliation":[{"name":"Pathology Unit, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8360-4376","authenticated-orcid":false,"given":"Delia","family":"Goletti","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases (INMI) \u201cLazzaro Spallanzani\u201d\u2014IRCCS, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/pim.12301","article-title":"The Intermediate Host Immune Response in Cystic Echinococcosis","volume":"38","author":"Tamarozzi","year":"2016","journal-title":"Parasite Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.exppara.2015.03.019","article-title":"The Laminated Layer: Recent Advances and Insights into Echinococcus Biology and Evolution","volume":"158","author":"Pittini","year":"2015","journal-title":"Exp. Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apar.2016.09.005","article-title":"Immunology of Alveolar and Cystic Echinococcosis (AE and CE)","volume":"96","author":"Gottstein","year":"2017","journal-title":"Adv. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hidalgo, C., Stoore, C., Strull, K., Franco, C., Corr\u00eaa, F., Jim\u00e9nez, M., Hern\u00e1ndez, M., Lorenzatto, K., Ferreira, H.B., and Galanti, N. (2019). New Insights of the Local Immune Response against Both Fertile and Infertile Hydatid Cysts. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211542"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0001-706X(02)00226-7","article-title":"Immunohistochemical Observations on Cellular Response in Unilocular Hydatid Lesions and Lymph Nodes of Cattle","volume":"85","author":"Sakamoto","year":"2003","journal-title":"Acta Trop."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19612","DOI":"10.1038\/s41598-019-56098-3","article-title":"The Local Immune Response during Echinococcus granulosus Growth in a Quantitative Hepatic Experimental Model","volume":"9","author":"Li","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1046\/j.1365-3024.1998.00180.x","article-title":"T-Cell Activity Associated with Secondary Infections and Implanted Cysts of Echinococcus granulosus in BALB\/c Mice","volume":"20","author":"Rogan","year":"1998","journal-title":"Parasite Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s12639-014-0593-5","article-title":"IL-4 Gene Expression in Adventitial Layer (Fibrous Layer) of Hepatic Ovine and Bovine Hydatid Cysts","volume":"40","author":"Dorosti","year":"2016","journal-title":"J. Parasit. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.vetpar.2015.02.027","article-title":"Immuno-Histochemical Study of Ovine Cystic Echinococcosis (Echinococcus granulosus) Shows Predominant T Cell Infiltration in Established Cysts","volume":"209","author":"Vismarra","year":"2015","journal-title":"Vet. Parasitol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"De Biase, D., Prisco, F., Pepe, P., Bosco, A., Piegari, G., d\u2019Aquino, I., Russo, V., Papparella, S., Maurelli, M.P., and Rinaldi, L. (2023). Evaluation of the Local Immune Response to Hydatid Cysts in Sheep Liver. Vet. Sci., 10.","DOI":"10.3390\/vetsci10050315"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Petrone, L., Vanini, V., Petruccioli, E., Ettorre, G.M., Schinin\u00e0, V., Busi Rizzi, E., Ludovisi, A., Corpolongo, A., Ippolito, G., and Pozio, E. (2015). Polyfunctional Specific Response to Echinococcus granulosus Associates to the Biological Activity of the Cysts. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004209"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vatankhah, A., Hal\u00e1sz, J., Piurk\u00f3, V., Barbai, T., R\u00e1s\u00f3, E., and T\u00edm\u00e1r, J. (2015). Characterization of the Inflammatory Cell Infiltrate and Expression of Costimulatory Molecules in Chronic Echinococcus granulosus Infection of the Human Liver. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1252-x"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"639362","DOI":"10.1155\/2012\/639362","article-title":"Host-Parasite Relationship in Cystic Echinococcosis: An Evolving Story","volume":"2012","author":"Siracusano","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.4254\/wjh.v6.i5.293","article-title":"Cystic Echinococcosis of the Liver: A Primer for Hepatologists","volume":"6","author":"Rinaldi","year":"2014","journal-title":"World J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1017\/S0022149X1800024X","article-title":"Immunohistochemical Observation of Local Inflammatory Cell Infiltration in the Host-Tissue Reaction Site of Human Hydatid Cysts","volume":"93","author":"Jafari","year":"2019","journal-title":"J. Helminthol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105306","DOI":"10.1016\/j.actatropica.2019.105306","article-title":"Potential Role of NF-\u03baB Pathway in the Immuno-Inflammatory Responses during Human Cystic Echinococcosis","volume":"203","author":"Tilioua","year":"2020","journal-title":"Acta Trop."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12839","DOI":"10.1111\/pim.12839","article-title":"Th1\/Th2\/Th17 Cytokine Profile in Hepatic Cystic Echinococcosis Patients with Different Cyst Stages","volume":"43","author":"Yasen","year":"2021","journal-title":"Parasite Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/bs.apar.2016.09.006","article-title":"The Echinococcoses: Diagnosis, Clinical Management and Burden of Disease","volume":"96","author":"Kern","year":"2017","journal-title":"Adv. Parasitol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actatropica.2009.11.001","article-title":"Writing Panel for the WHO-IWGE Expert Consensus for the Diagnosis and Treatment of Cystic and Alveolar Echinococcosis in Humans","volume":"114","author":"Brunetti","year":"2010","journal-title":"Acta Trop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e12809","DOI":"10.1111\/pim.12809","article-title":"Soluble Programmed Death-1 (sPD-1) as Predictor of Early Surgical Outcomes of Paediatric Cystic Echinococcosis","volume":"43","author":"Sakly","year":"2021","journal-title":"Parasite Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shafiei, R., Mohajerzadeh, M.S., Masomi, H.F.A., Tavakoli, M., Turki, H., and Firouzeh, N. (2024). Discordance Therapeutic Protocol of Cystic Echinococcosis with WHO Guideline: A Descriptive Study Based on Liver Ultra-Sonographic Data in North Khorasan Province, Northeastern of Iran. J. Ultrasound Med.","DOI":"10.1002\/jum.16452"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/nbm.1252","article-title":"Metabolic Viability Assessment of Cystic Echinococcosis Using High-Field 1H MRS of Cyst Contents","volume":"21","author":"Hosch","year":"2008","journal-title":"NMR Biomed."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pagnozzi, D., Addis, M.F., Biosa, G., Roggio, A.M., Tedde, V., Mariconti, M., Tamarozzi, F., Meroni, V., Masu, G., and Masala, G. (2016). Diagnostic Accuracy of Antigen 5-Based ELISAs for Human Cystic Echinococcosis. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004585"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4269\/ajtmh.15-0219","article-title":"Factors Influencing the Serological Response in Hepatic Echinococcus granulosus Infection","volume":"94","author":"Lissandrin","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Gonz\u00e1lez, A., Gonz\u00e1lez-Bertol\u00edn, B., Urrea, L., Fleury, A., Ferrer, E., Siles-Lucas, M., Tamarozzi, F., and Perteguer, M.J. (2022). Multiple-Bead Assay for the Differential Serodiagnosis of Neglected Human Cestodiases: Neurocysticercosis and Cystic Echinococcosis. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010109"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1017\/S0022149X2400021X","article-title":"Ultrasound Diagnosis of Cystic Echinococcosis: Updates and Implications for Clinical Management","volume":"98","author":"Tamarozzi","year":"2024","journal-title":"J. Helminthol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/QCO.0000000000000941","article-title":"\u201cNo Cyst, No Echinococcosis\u201d: A Scoping Review Update on the Diagnosis of Cystic Echinococcosis after the Issue of the WHO-IWGE Expert Consensus and Current Perspectives","volume":"36","author":"Uchiumi","year":"2023","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e12499","DOI":"10.1111\/pim.12499","article-title":"A T-Cell Diagnostic Test for Cystic Echinococcosis Based on Antigen B Peptides","volume":"39","author":"Petrone","year":"2017","journal-title":"Parasite Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jinf.2014.10.009","article-title":"IL-4 Specific-Response in Whole Blood Associates with Human Cystic Echinococcosis and Cyst Activity","volume":"70","author":"Petrone","year":"2015","journal-title":"J. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12695","DOI":"10.1111\/pim.12695","article-title":"Species Specificity Preliminary Evaluation of an IL-4-Based Test for the Differential Diagnosis of Human Echinococcosis","volume":"42","author":"Petrone","year":"2020","journal-title":"Parasite Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Batisti Biffignandi, G., Vola, A., Sassera, D., Najafi-Fard, S., Gomez Morales, M.A., Brunetti, E., Teggi, A., Goletti, D., Petrone, L., and Tamarozzi, F. (2023). Antigen Discovery by Bioinformatics Analysis and Peptide Microarray for the Diagnosis of Cystic Echinococcosis. PLoS Negl. Trop. Dis., 17.","DOI":"10.1371\/journal.pntd.0011210"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"286.e7","DOI":"10.1016\/j.cmi.2020.09.051","article-title":"A Whole Blood Test to Measure SARS-CoV-2-Specific Response in COVID-19 Patients","volume":"27","author":"Petrone","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jinf.2021.02.023","article-title":"In-Vitro Evaluation of the Immunomodulatory Effects of Baricitinib: Implication for COVID-19 Therapy","volume":"82","author":"Petrone","year":"2021","journal-title":"J. Infect."},{"key":"ref_34","unstructured":"(2024, May 14). Meeting of the WHO Informal Working Group on Echinococcosis (WHO-IWGE) WHO Headquarters, Geneva, Switzerland 15\u201316 December 2016. Available online: https:\/\/www.who.int\/publications-detail-redirect\/WHO-HTM-NTD-NZD-2017.01."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13071-022-05197-8","article-title":"Species and Genotypes Belonging to Echinococcus granulosus Sensu Lato Complex Causing Human Cystic Echinococcosis in Europe (2000\u20132021): A Systematic Review","volume":"15","author":"Casulli","year":"2022","journal-title":"Parasit Vectors"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:53:49Z","timestamp":1760108029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,4]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["pathogens13060477"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13060477","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2024,6,4]]}}}