title: Systems parasitology: effects of Fasciola hepatica on the neurochemical profile in the rat brain.
abstract: We characterize the integrated response of a rat host to the liver fluke Fasciola hepatica using a combination of (1)H nuclear magnetic resonance spectroscopic profiles (liver, kidney, intestine, brain, spleen, plasma, urine, feces) and multiplex cytokine markers of systemic inflammation. Multivariate mathematical models were built to describe the main features of the infection at the systems level. In addition to the expected modulation of hepatic choline and energy metabolism, we found significant perturbations of the nucleotide balance in the brain, together with increased plasma IL-13, suggesting a shift toward modulation of immune reactions to minimize inflammatory damage, which may favor the co-existence of the parasite in the host. Subsequent analysis of brain extracts from other trematode infection models (i.e. Schistosoma mansoni, and Echinostoma caproni) did not elicit a change in neural nucleotide levels, indicating that the neural effects of F. hepatica infection are specific. We propose that the topographically extended response to invasion of the host as characterized by the modulated global metabolic phenotype is stratified across several bio-organizational levels and reflects the direct manipulation of host-nucleotide balance.
authors.affiliation: Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK. jasmina.saric@imperial.ac.uk
authors.forename: Jasmina
authors.initials: J
authors.lastname: Saric
authors.forename: Jia V
authors.initials: JV
authors.lastname: Li
authors.forename: Jürg
authors.initials: J
authors.lastname: Utzinger
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: Olaf
authors.initials: O
authors.lastname: Beckonert
authors.forename: Mansour T A
authors.initials: MT
authors.lastname: Sharabiani
authors.forename: Judith M
authors.initials: JM
authors.lastname: Fonville
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D002794:Choline / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004449:Echinostoma / Q000472:pathogenicity; D004734:Energy Metabolism; D005210:Fasciola hepatica / Q000472:pathogenicity*; D005260:Female; D006790:Host-Parasite Interactions; D018836:Inflammation Mediators / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D015233:Models, Statistical; D009711:Nucleotides / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012550:Schistosoma mansoni / Q000472:pathogenicity; D049490:Systems Biology; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009711:Nucleotides; D002794:Choline