Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica

被引:19
作者
Chuah, Candy [1 ,2 ,3 ]
Jones, Malcolm K. [2 ]
McManus, Donald P. [1 ]
Nawaratna, Sujeevi K. [1 ]
Burke, Melissa L. [1 ,4 ]
Owen, Helen C. [2 ]
Ramm, Grant A. [1 ]
Gobert, Geoffrey N. [1 ]
机构
[1] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia
[2] Univ Queensland, Sch Vet Sci, Gatton, Qld 4343, Australia
[3] Univ Sains Malaysia, Sch Med Sci, Kelantan 16150, Malaysia
[4] EMBL EBI, European Mol Biol Lab, European Bioinformat Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SD, England
基金
英国医学研究理事会;
关键词
Schistosomiasis; Hepatic fibrosis; Helminth; Transcriptomics; Liver recovery; PROLIFERATOR-ACTIVATED RECEPTORS; HEPATIC-FIBROSIS; DIFFERENTIAL EXPRESSION; NEUTROPHIL RECRUITMENT; DENDRITIC CELLS; PPAR-ALPHA; PRAZIQUANTEL; CHEMOKINE; MANSONI; GENES;
D O I
10.1016/j.ijpara.2015.12.004
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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. (C) 2016 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:239 / 252
页数:14
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