title: Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica.
abstract: For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia; School of Veterinary Sciences, The University of Queensland, Gatton, Qld 4343, Australia; School of Medical Sciences, Universiti Sains Malaysia, 16150 Kelantan, Malaysia.
authors.forename: Candy
authors.initials: C
authors.lastname: Chuah
authors.affiliation: School of Veterinary Sciences, The University of Queensland, Gatton, Qld 4343, Australia.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Jones
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia.
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia.
authors.forename: Sujeevi K
authors.initials: SK
authors.lastname: Nawaratna
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Burke
authors.affiliation: School of Veterinary Sciences, The University of Queensland, Gatton, Qld 4343, Australia.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Owen
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Ramm
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia. Electronic address: Geoffrey.Gobert@qimrberghofer.edu.au.
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Gobert
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006099:Granuloma / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009504:Neutrophils / Q000473:pathology; D011223:Praziquantel / Q000627:therapeutic use*; D018510:RNA, Helminth / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D012549:Schistosoma japonicum / Q000235:genetics / Q000302:isolation & purification; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000473:pathology; D013154:Spleen / Q000473:pathology; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000871:Anthelmintics; D018510:RNA, Helminth; D011223:Praziquantel
keywords: Helminth; Hepatic fibrosis; Liver recovery; Schistosomiasis; Transcriptomics