Live imaging of collagen deposition during experimental hepatic schistosomiasis and recovery: a view on a dynamic process

Abstract

Hepatic fibrosis is the central cause of chronic clinical pathology resulting from infection by the blood flukes Schistosoma japonicum or S. mansoni. Much has been elucidated regarding the molecular, cellular and immunological responses that correspond to the formation of the granulomatous response to trapped schistosome eggs. A central feature of this Th2 response is the deposition of collagen around the periphery of the granuloma. To date, traditional histology and transcriptional methods have been used to quantify the deposition of collagen and to monitor the formation of the hepatic granuloma during experimental animal models of schistosomiasis. We have investigated the dynamic nature of granuloma formation through the use of a transgenic mouse model (B6.Collagen 1(A) luciferase mice (B6.Coll 1A-luc +)). With this model and whole animal bioluminescence imaging, we followed the deposition of collagen during an active schistosome 2 infection with Chinese and Philippines geographical strains of S. japonicum and after clearance of the adult parasites by the drug praziquantel. Individual mice were re-imaged over the time course to provide robust real-time quantitation of the development of chronic fibrotic disease. This model provides an improved method to follow the course of hepatic schistosomiasis-induced hepatic pathology and effectively supports the current dogma of the formation of hepatic fibrosis, originally elucidated from static traditional histology. This study demonstrates the first use of the B6.Coll 1Aluc + mouse to monitor the dynamics of disease development and the treatment of pathogen-induced infection with the underlying pathology of fibrosis.

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

“…Quantification of microvessel density was performed on CD31 stained tissues, submesothelial area reaching to the muscle was annotated as region of interest (ROI) and microvessel algorithm v1 (Image Scope, Leica, Wetzlar, Germany) was used. Fibrosis was analyzed on Sirius red staining as described previously [43] after validation of thresholds, collagen deposition is expressed in percentage submesothelial positive area. Immunohistochemical stainings were evaluated using the Aperio Positive Pixel Count Algorithm (version 9) for quantification of the amounts of positive pixels per scanned virtual slide.…”

Clinical and Preclinical Imaging of Hepatosplenic Schistosomiasis

“…Bioluminescence imaging (BLI), a method allowing direct visualisation of gene expression through chemically-induced light emission [88,89] was used to follow up eosinophilia and eosinopoiesis in mice infected with S. mansoni and expressing a luciferase reporter driven by an eosinophil peroxidase promoter [90]. In another study, the dynamics of collagen deposition in S. japonicum infection were monitored in mice expressing luciferase under a collagen promotor [91]. Newly formed collagen was assessed in mice with and without praziquantel treatment after granuloma formation.…”