{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:51:21Z","timestamp":1787316681720,"version":"build-2736575974"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":3538,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000163","name":"ARC Discovery","doi-asserted-by":"publisher","award":["DP1093471"],"award-info":[{"award-number":["DP1093471"]}],"id":[{"id":"10.13039\/100000163","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The severity of schistosome egg-induced hepatic granulomatous pathology depends markedly on the nature of the host immune responses. In this study, we used LMM and microarray analysis to compare gene expression profiles of histologically distinct zones within, and directly proximal to, hepatic granulomas that developed in C57BL\/6 mice infected with Schistosoma japonicum. There was significant up-regulation of type-1, type-2, and type-17 immune-associated genes within the granuloma core (adjacent to eggs), followed by increased expression of type-2 and fibrotic genes at the outer zones of granulomas. Neutrophil-associated genes were also found to be expressed differentially in the core and at the peripheral zone of granulomas, present at 7 weeks p.i., demonstrating a significant role of neutrophils in S. japonicum granulomatous pathology. The release of NETs was observed microscopically in granulomas obtained from the livers of infected mice and when human neutrophils were incubated in vitro in the presence of S. japonicum eggs. These finding are the first to suggest a novel, dual role for neutrophils in the mediation of tissue damage and repair in S. japonicum egg-induced hepatic granulomatous lesions. Together, these results provide an overview of the local events occurring within the granuloma microenvironment.<\/jats:p>","DOI":"10.1189\/jlb.1212653","type":"journal-article","created":{"date-parts":[[2013,5,25]],"date-time":"2013-05-25T01:44:55Z","timestamp":1369446295000},"page":"353-365","source":"Crossref","is-referenced-by-count":77,"title":["Spatial and temporal transcriptomics of\n                    <i>Schistosoma japonicum<\/i>\n                    -induced hepatic granuloma formation reveals novel roles for neutrophils"],"prefix":"10.1093","volume":"94","author":[{"given":"Candy","family":"Chuah","sequence":"first","affiliation":[{"name":"Parasite Cell Biology, Queensland Institute of Medical Research , Brisbane, Australia"},{"name":"School of Veterinary Sciences, The University of Queensland , Gatton, Australia"},{"name":"School of Medical Sciences, Universiti Sains Malaysia , Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm K","family":"Jones","sequence":"additional","affiliation":[{"name":"Parasite Cell Biology, Queensland Institute of Medical Research , Brisbane, Australia"},{"name":"School of Veterinary Sciences, The University of Queensland , Gatton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa L","family":"Burke","sequence":"additional","affiliation":[{"name":"Division of Mycobacterial Research, National Institute for Medical Research , London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C","family":"Owen","sequence":"additional","affiliation":[{"name":"School of Veterinary Sciences, The University of Queensland , Gatton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrie J","family":"Anthony","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratories, Queensland Institute of Medical Research , Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald P","family":"McManus","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratories, Queensland Institute of Medical Research , Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant A","family":"Ramm","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group, Queensland Institute of Medical Research , Brisbane, Australia"},{"name":"Faculty of Health Sciences, The University of Queensland , Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey N","family":"Gobert","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratories, Queensland Institute of Medical Research , Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,5,24]]},"reference":[{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1056\/NEJMra012396","article-title":"Schistosomiasis","volume":"346","author":"Ross","year":"2002","journal-title":"N. 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Prot."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2353\/ajpath.2007.061033","article-title":"A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria","volume":"171","author":"Amante","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1471-2164-8-379","article-title":"Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse","volume":"8","author":"Rodriguez","year":"2007","journal-title":"BMC Genomics"},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.4049\/jimmunol.171.7.3655","article-title":"Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair","volume":"171","author":"Sandler","year":"2003","journal-title":"J. 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Rev. Immunol."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1749-6632.1997.tb46251.x","article-title":"Cytokine expression and release by neutrophils","volume":"832","author":"Cassatella","year":"1997","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0006-291X(02)02748-1","article-title":"The bovine lactoferrin region responsible for promoting the collagen gel contractile activity of human fibroblasts","volume":"299","author":"Takayama","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nri1841","article-title":"Neutrophil serine proteases: specific regulators of inflammation","volume":"6","author":"Pham","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1517\/14728222.12.2.145","article-title":"Targeting neutrophil elastase in cystic fibrosis","volume":"12","author":"Kelly","year":"2008","journal-title":"Expert Opin. Ther. Targets"},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"6579","DOI":"10.1016\/S0021-9258(18)68680-6","article-title":"H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen","volume":"263","author":"Collier","year":"1988","journal-title":"J. Biol. Chem."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/jlb.61.6.695","article-title":"Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils","volume":"61","author":"Sallenave","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1164\/ajrccm.164.5.2103040","article-title":"Leukocyte elastase: physiological functions and role in acute lung injury","volume":"164","author":"Lee","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/j.1462-5822.2005.00659.x","article-title":"Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms","volume":"8","author":"Urban","year":"2006","journal-title":"Cell. Microbiol."},{"key":"2023032800062472500_","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.1073\/pnas.0900226106","article-title":"Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps","volume":"106","author":"Guimaraes-Costa","year":"2009","journal-title":"Proc. Natl. Acad. Sci. 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