{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:39:22Z","timestamp":1767166762897,"version":"build-2238731810"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T00:00:00Z","timestamp":1513641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"EU consortium PARAVAC","award":["FPVII-KBBE-2010-4-265862"],"award-info":[{"award-number":["FPVII-KBBE-2010-4-265862"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Fasciola hepatica<\/jats:named-content>\n                    is a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response to\n                    <jats:named-content content-type=\"genus-species\">F. hepatica<\/jats:named-content>\n                    following natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed to\n                    <jats:named-content content-type=\"genus-species\">F. hepatica<\/jats:named-content>\n                    infection. Cohorts of replacement dairy heifer calves (\n                    <jats:italic>n<\/jats:italic>\n                    = 42) with no prior exposure to\n                    <jats:named-content content-type=\"genus-species\">F. hepatica<\/jats:named-content>\n                    , on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through an\n                    <jats:named-content content-type=\"genus-species\">F. hepatica<\/jats:named-content>\n                    -specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed-effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite-specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-\u03b3) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge with\n                    <jats:named-content content-type=\"genus-species\">F. hepatica<\/jats:named-content>\n                    . This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens.\n                  <\/jats:p>","DOI":"10.1128\/iai.00607-17","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T20:50:17Z","timestamp":1507582217000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Dairy Heifers Naturally Exposed to Fasciola hepatica Develop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation"],"prefix":"10.1128","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7305-5262","authenticated-orcid":false,"given":"John","family":"Graham-Brown","sequence":"first","affiliation":[{"name":"Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Hartley","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Clough","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aras","family":"Kadioglu","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Baylis","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"},{"name":"National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8186-7236","authenticated-orcid":false,"given":"Diana J. L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","first-page":"377","volume-title":"Fasciolosis","author":"Spithill TW","year":"1999","unstructured":"Spithill TW, Smooker PM, Sexton JL, Bozas E, Morrison CA, Creaney J, Parsons JC. 1999. Development of vaccines against Fasciola hepatica, p 377\u2013410. In Dalton JP (ed), Fasciolosis. CABI Publishing, Wallingford, United Kingdom."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2006.09.010"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2015.05.013"},{"key":"e_1_3_4_5_2","first-page":"341","volume-title":"Fasciolosis","author":"Mulcahy G","year":"1999","unstructured":"Mulcahy G, Joyce P, Dalton JP. 1999. Immunology of Fasciola hepatica infection, p 341\u2013375. In Dalton JP (ed), Fasciolosis. CABI Publishing, Wallingford, United Kingdom."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.4081\/gh.2015.352"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.113.14.315"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-0813.1995.tb03546.x"},{"key":"e_1_3_4_9_2","first-page":"399","article-title":"Triclabendazole-resistant liver fluke in Scottish sheep","volume":"143","author":"Mitchell GB","year":"1998","unstructured":"Mitchell GB, Maris L, Bonniwell MA. 1998. Triclabendazole-resistant liver fluke in Scottish sheep. Vet Rec 143:399.","journal-title":"Vet Rec"},{"key":"e_1_3_4_10_2","first-page":"200","article-title":"Triclabendazole-resistant Fasciola hepatica in southwest Wales","volume":"146","author":"Thomas I","year":"2000","unstructured":"Thomas I, Coles GC, Duffus K. 2000. Triclabendazole-resistant Fasciola hepatica in southwest Wales. Vet Rec 146:200.","journal-title":"Vet Rec"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4017(00)00267-3"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2010.12.047"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2013.01.001"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2015.01.004"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2014.07.011"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.06.039"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1053\/rvsc.1998.0270"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep23345"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)00289-2"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4017(89)90162-3"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4017(95)00858-6"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3024.2003.00627.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5288(98)90171-0"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1985.tb00095.x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4017(99)00200-9"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(98)00207-4"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4017(99)00177-6"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2008.05.008"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2013.03.035"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2013.04.008"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5288(18)32798-X"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12326"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1865-1682.2009.01075.x"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.3.818-827.1994"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01445-06"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5288(95)90122-1"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-1571(66)90004-5"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2009.01135.x"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9975(66)90049-1"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00732-07"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830200415"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.156.23.729"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2004.08.005"},{"key":"e_1_3_4_44_2","volume-title":"AHVLA standard operating procedure, SOP PA026, fluke egg demonstration by sedimentation","author":"Anonymous","year":"2007","unstructured":"Anonymous. 2007. AHVLA standard operating procedure, SOP PA026, fluke egg demonstration by sedimentation. Animal Health and Veterinary Laboratories Agency, Weybridge, United Kingdom."},{"key":"e_1_3_4_45_2","volume-title":"Diagnosing helminthiasis by coprological examination","author":"Thienpont D","year":"1986","unstructured":"Thienpont D, Rochette R, Vanparjis OFJ. 1986. Diagnosing helminthiasis by coprological examination, 2nd ed. Janssen Research Foundation, Beerse, Belgium.","edition":"2"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.12.5.695-699.1980"},{"key":"e_1_3_4_47_2","volume-title":"Endotoxins and cell culture; technical bulletin","author":"Ryan J","year":"2008","unstructured":"Ryan J. 2008. Endotoxins and cell culture; technical bulletin. Corning Life Sciences, Lowell, MA."},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2007.00936.x"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2427(91)90078-Q"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2427(91)90082-N"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2427(90)90042-Q"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(02)00007-7"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.6702"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2010.2367"},{"key":"e_1_3_4_55_2","volume-title":"nlme: linear and nonlinear mixed effects models","author":"Pinheiro J","year":"2016","unstructured":"Pinheiro J, Bates D, DebRoy S, Sarkar D, R Core Team. 2016. nlme: linear and nonlinear mixed effects models. R Foundation for Statistical Computing, Vienna, Austria."},{"key":"e_1_3_4_56_2","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2013","unstructured":"R Core Team. 2013. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria."},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.2517-6161.1964.tb00553.x","article-title":"An analysis of transformations","volume":"26","author":"Box GE","year":"1964","unstructured":"Box GE, Cox DR. 1964. An analysis of transformations. J R Stat Soc Series B Stat Methodol 26:211\u2013252.","journal-title":"J R Stat Soc Series B Stat Methodol"},{"key":"e_1_3_4_58_2","volume-title":"Linear models with R","author":"Faraway JJ","year":"2005","unstructured":"Faraway JJ. 2005. Linear models with R. CRC Press, Boca Raton, FL."},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1109\/TAC.1974.1100705"},{"key":"e_1_3_4_60_2","volume-title":"A handbook of statistical analyses using R","author":"Everitt B","year":"2010","unstructured":"Everitt B, Hothorn T. 2010. A handbook of statistical analyses using R, 2nd ed (electronic). CRC Press, Boca Raton, FL.","edition":"2"}],"updated-by":[{"DOI":"10.1128\/iai.00247-18","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000}}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00607-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00607-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T12:12:30Z","timestamp":1719490350000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00607-17"}},"subtitle":[],"editor":[{"given":"Guy H.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1128\/IAI.00607-17"],"URL":"https:\/\/doi.org\/10.1128\/iai.00607-17","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"2017-09-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00607-17"}}