Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents
Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents
Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei-mouse, Trypanosoma brucei brucei-mouse, Schistosoma mansoni-mouse, and Fasciola hepatica-rat were statistically coanalyzed. (1)H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the 'Meso Scale Discovery' multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-gamma, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and d-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single- and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways.
Animals, Cytokines/metabolism, Discriminant Analysis, Disease Models, Animal, Fasciola hepatica/physiology, Female, Histocytochemistry, Host-Parasite Interactions, Metabolome, Mice, Multivariate Analysis, Nuclear Magnetic Resonance, Biomolecular, Parasitic Diseases/blood, Phenotype, Plasmodium berghei/physiology, Principal Component Analysis, Rats, Schistosoma mansoni/physiology, Trypanosoma brucei brucei/physiology
2255-2264
Saric, Jasmina
ff088cb0-8e3b-41df-86f3-5ad33c9f99a0
Li, Jia V
ad266e35-53c1-45c3-9756-4fb6b0386e1c
Swann, Jonathan R
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Utzinger, Jürg
e7cb2474-a99f-41a7-b680-a873faccb703
Calvert, Gail
5bdaf1bb-6e67-4385-b352-4fffc33455dc
Nicholson, Jeremy K
72991774-7e08-4592-ae57-e7dcc2ec158e
Dirnhofer, Stephan
b16ae644-9407-4ac4-8c3e-4425dce4d9f8
Dallman, Maggie J
19834741-cca3-43a7-8067-3790116deeba
Bictash, Magda
c045146d-0dca-4436-83cd-06bb77e5a87a
Holmes, Elaine
d3b92a6b-1c3f-4758-b653-ba35afd3f57d
7 May 2010
Saric, Jasmina
ff088cb0-8e3b-41df-86f3-5ad33c9f99a0
Li, Jia V
ad266e35-53c1-45c3-9756-4fb6b0386e1c
Swann, Jonathan R
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Utzinger, Jürg
e7cb2474-a99f-41a7-b680-a873faccb703
Calvert, Gail
5bdaf1bb-6e67-4385-b352-4fffc33455dc
Nicholson, Jeremy K
72991774-7e08-4592-ae57-e7dcc2ec158e
Dirnhofer, Stephan
b16ae644-9407-4ac4-8c3e-4425dce4d9f8
Dallman, Maggie J
19834741-cca3-43a7-8067-3790116deeba
Bictash, Magda
c045146d-0dca-4436-83cd-06bb77e5a87a
Holmes, Elaine
d3b92a6b-1c3f-4758-b653-ba35afd3f57d
Saric, Jasmina, Li, Jia V, Swann, Jonathan R, Utzinger, Jürg, Calvert, Gail, Nicholson, Jeremy K, Dirnhofer, Stephan, Dallman, Maggie J, Bictash, Magda and Holmes, Elaine
(2010)
Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents.
Journal of Proteome Research, 9 (5), .
(doi:10.1021/pr901019z).
Abstract
Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei-mouse, Trypanosoma brucei brucei-mouse, Schistosoma mansoni-mouse, and Fasciola hepatica-rat were statistically coanalyzed. (1)H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the 'Meso Scale Discovery' multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-gamma, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and d-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single- and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways.
This record has no associated files available for download.
More information
e-pub ahead of print date: 22 January 2010
Published date: 7 May 2010
Keywords:
Animals, Cytokines/metabolism, Discriminant Analysis, Disease Models, Animal, Fasciola hepatica/physiology, Female, Histocytochemistry, Host-Parasite Interactions, Metabolome, Mice, Multivariate Analysis, Nuclear Magnetic Resonance, Biomolecular, Parasitic Diseases/blood, Phenotype, Plasmodium berghei/physiology, Principal Component Analysis, Rats, Schistosoma mansoni/physiology, Trypanosoma brucei brucei/physiology
Identifiers
Local EPrints ID: 439400
URI: http://eprints.soton.ac.uk/id/eprint/439400
ISSN: 1535-3893
PURE UUID: 7252de70-d5e1-4f21-afa6-483cfef3bbf0
Catalogue record
Date deposited: 21 Apr 2020 16:52
Last modified: 17 Mar 2024 04:00
Export record
Altmetrics
Contributors
Author:
Jasmina Saric
Author:
Jia V Li
Author:
Jürg Utzinger
Author:
Gail Calvert
Author:
Jeremy K Nicholson
Author:
Stephan Dirnhofer
Author:
Maggie J Dallman
Author:
Magda Bictash
Author:
Elaine Holmes
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics