Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts
Cystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease res...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2015-11, Vol.9 (11), p.e0004209-e0004209 |
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| creator | Petrone, Linda Vanini, Valentina Petruccioli, Elisa Ettorre, Giuseppe Maria Schininà, Vincenzo Busi Rizzi, Elisa Ludovisi, Alessandra Corpolongo, Angela Ippolito, Giuseppe Pozio, Edoardo Teggi, Antonella Goletti, Delia |
| description | Cystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease resistance, whereas Th2 cytokines are related to disease susceptibility and chronicity. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures.
We enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the "active stages" group compared to the "inactive stages" group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE.
We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence. |
| doi_str_mv | 10.1371/journal.pntd.0004209 |
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We enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the "active stages" group compared to the "inactive stages" group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE.
We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0004209</identifier><identifier>PMID: 26575186</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Animals ; Antigens ; Biological activity ; CD4-Positive T-Lymphocytes - immunology ; Cysts ; Cytokines ; Cytokines - metabolism ; Development and progression ; Echinococcosis ; Echinococcosis - immunology ; Echinococcus granulosus - immunology ; Female ; Flow Cytometry ; Humans ; Immune response ; Male ; Middle Aged ; Observations ; Parasites ; Parasitic diseases ; Properties ; Prospective Studies ; Studies ; T-Lymphocyte Subsets - immunology ; Zoonoses</subject><ispartof>PLoS neglected tropical diseases, 2015-11, Vol.9 (11), p.e0004209-e0004209</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Petrone et al 2015 Petrone et al</rights><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Petrone L, Vanini V, Petruccioli E, Ettorre GM, Schininà V, Busi Rizzi E, et al. (2015) Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts. PLoS Negl Trop Dis 9(11): e0004209. doi:10.1371/journal.pntd.0004209</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c596t-dd22a31b3ca6b0eb478b2211ebd9bbbbbb8dcbb788a4df250d65a8b4dca4a8013</citedby><cites>FETCH-LOGICAL-c596t-dd22a31b3ca6b0eb478b2211ebd9bbbbbb8dcbb788a4df250d65a8b4dca4a8013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648505/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648505/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27902,27903,53768,53770,79345,79346</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26575186$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Taylan Ozkan, Aysegul</contributor><creatorcontrib>Petrone, Linda</creatorcontrib><creatorcontrib>Vanini, Valentina</creatorcontrib><creatorcontrib>Petruccioli, Elisa</creatorcontrib><creatorcontrib>Ettorre, Giuseppe Maria</creatorcontrib><creatorcontrib>Schininà, Vincenzo</creatorcontrib><creatorcontrib>Busi Rizzi, Elisa</creatorcontrib><creatorcontrib>Ludovisi, Alessandra</creatorcontrib><creatorcontrib>Corpolongo, Angela</creatorcontrib><creatorcontrib>Ippolito, Giuseppe</creatorcontrib><creatorcontrib>Pozio, Edoardo</creatorcontrib><creatorcontrib>Teggi, Antonella</creatorcontrib><creatorcontrib>Goletti, Delia</creatorcontrib><title>Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Cystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease resistance, whereas Th2 cytokines are related to disease susceptibility and chronicity. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures.
We enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the "active stages" group compared to the "inactive stages" group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE.
We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence.</description><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Antigens</subject><subject>Biological activity</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cysts</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Development and progression</subject><subject>Echinococcosis</subject><subject>Echinococcosis - immunology</subject><subject>Echinococcus granulosus - immunology</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immune response</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Observations</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Properties</subject><subject>Prospective Studies</subject><subject>Studies</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Zoonoses</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNptkl1r2zAUhs3YWLtu_2BshsHYTTJJ1pdvBlnoukJhYx_XQpKlREGRUksu5N9PTtySwOwLC-k5j44Pb1W9hWAOGwY_b-LQB-nnu5C7OQAAI9A-qy5h25AZYg15frK-qF6ltAGAtITDl9UFooQRyOllFX5Gv7dD0NnFYqt_74x21un6l0m7GJKpc6yv9dqFqKPWQ6pvehkGH1NZLlKK2sls0kjltam_uujjyuliWhTlg8v7OtrD0XKfcnpdvbDSJ_Nm-l5Vf79d_1l-n939uLldLu5mmrQ0z7oOIdlA1WhJFTAKM64QgtCorlWHh3daKca5xJ1FBHSUSK5wpyWWHMDmqnp_9O5Kp2IaVRKQ4ZY246gKcXskuig3Yte7rez3IkonDhuxXwnZZ6e9EQhbplumIWkMppgqimWrrLUYkpZrVlxfptsGtTWdNiH30p9Jz0-CW4tVfBDFxgkgRfBpEvTxfjApi61L2ngvg4nD2HdDWsAApAX9cERXsrTmgo3FqEdcLHBDW44oQ4Wa_4cqb2e2TsdgrCv7ZwUfTwrWRvq8TtEPYyzSOYiPoO5jSr2xT78JgRiD-ThtMQZTTMEsZe9OR_RU9JjE5h9Vo-L1</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Petrone, Linda</creator><creator>Vanini, Valentina</creator><creator>Petruccioli, Elisa</creator><creator>Ettorre, Giuseppe Maria</creator><creator>Schininà, Vincenzo</creator><creator>Busi Rizzi, Elisa</creator><creator>Ludovisi, Alessandra</creator><creator>Corpolongo, Angela</creator><creator>Ippolito, Giuseppe</creator><creator>Pozio, Edoardo</creator><creator>Teggi, Antonella</creator><creator>Goletti, Delia</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20151101</creationdate><title>Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts</title><author>Petrone, Linda ; Vanini, Valentina ; Petruccioli, Elisa ; Ettorre, Giuseppe Maria ; Schininà, Vincenzo ; Busi Rizzi, Elisa ; Ludovisi, Alessandra ; Corpolongo, Angela ; Ippolito, Giuseppe ; Pozio, Edoardo ; Teggi, Antonella ; Goletti, Delia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c596t-dd22a31b3ca6b0eb478b2211ebd9bbbbbb8dcbb788a4df250d65a8b4dca4a8013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Antigens</topic><topic>Biological activity</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cysts</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Development and progression</topic><topic>Echinococcosis</topic><topic>Echinococcosis - immunology</topic><topic>Echinococcus granulosus - immunology</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Immune response</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Observations</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Properties</topic><topic>Prospective Studies</topic><topic>Studies</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>Zoonoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petrone, Linda</creatorcontrib><creatorcontrib>Vanini, Valentina</creatorcontrib><creatorcontrib>Petruccioli, Elisa</creatorcontrib><creatorcontrib>Ettorre, Giuseppe Maria</creatorcontrib><creatorcontrib>Schininà, Vincenzo</creatorcontrib><creatorcontrib>Busi Rizzi, Elisa</creatorcontrib><creatorcontrib>Ludovisi, Alessandra</creatorcontrib><creatorcontrib>Corpolongo, Angela</creatorcontrib><creatorcontrib>Ippolito, Giuseppe</creatorcontrib><creatorcontrib>Pozio, Edoardo</creatorcontrib><creatorcontrib>Teggi, Antonella</creatorcontrib><creatorcontrib>Goletti, Delia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petrone, Linda</au><au>Vanini, Valentina</au><au>Petruccioli, Elisa</au><au>Ettorre, Giuseppe Maria</au><au>Schininà, Vincenzo</au><au>Busi Rizzi, Elisa</au><au>Ludovisi, Alessandra</au><au>Corpolongo, Angela</au><au>Ippolito, Giuseppe</au><au>Pozio, Edoardo</au><au>Teggi, Antonella</au><au>Goletti, Delia</au><au>Taylan Ozkan, Aysegul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2015-11-01</date><risdate>2015</risdate><volume>9</volume><issue>11</issue><spage>e0004209</spage><epage>e0004209</epage><pages>e0004209-e0004209</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Cystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease resistance, whereas Th2 cytokines are related to disease susceptibility and chronicity. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures.
We enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the "active stages" group compared to the "inactive stages" group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE.
We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26575186</pmid><doi>10.1371/journal.pntd.0004209</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Animals Antigens Biological activity CD4-Positive T-Lymphocytes - immunology Cysts Cytokines Cytokines - metabolism Development and progression Echinococcosis Echinococcosis - immunology Echinococcus granulosus - immunology Female Flow Cytometry Humans Immune response Male Middle Aged Observations Parasites Parasitic diseases Properties Prospective Studies Studies T-Lymphocyte Subsets - immunology Zoonoses |
| title | Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts |
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