A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model.
The helminth Ascaris causes ascariasis in both humans and pigs. Humans, especially children, experience significant morbidity including respiratory complications, growth deficits and intestinal obstruction. Given that 800 million people worldwide are infected by Ascaris, this represents a significan...
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ftdoajarticles:oai:doaj.org/article:2b76ff06b07a4a9ea8b02d604fa8a3a7 2023-05-15T15:11:49+02:00 A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model. Gwendoline Deslyper Thomas J Colgan Andrew J R Cooper Celia V Holland James C Carolan 2016-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004837 https://doaj.org/article/2b76ff06b07a4a9ea8b02d604fa8a3a7 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4974003?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004837 https://doaj.org/article/2b76ff06b07a4a9ea8b02d604fa8a3a7 PLoS Neglected Tropical Diseases, Vol 10, Iss 8, p e0004837 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004837 2022-12-31T14:27:54Z The helminth Ascaris causes ascariasis in both humans and pigs. Humans, especially children, experience significant morbidity including respiratory complications, growth deficits and intestinal obstruction. Given that 800 million people worldwide are infected by Ascaris, this represents a significant global public health concern. The severity of the symptoms and associated morbidity are related to the parasite burden and not all hosts are infected equally. While the pathology of the disease has been extensively examined, our understanding of the molecular mechanisms underlying resistance and susceptibility to this nematode infection is poor. In order to investigate host differences associated with heavy and light parasite burden, an experimental murine model was developed utilising Ascaris-susceptible and -resistant mice strains, C57BL/6J and CBA/Ca, respectively, which experience differential burdens of migratory Ascaris larvae in the host lungs. Previous studies identified the liver as the site where this difference in susceptibility occurs. Using a label free quantitative proteomic approach, we analysed the hepatic proteomes of day four post infection C57BL/6J and CBA/Ca mice with and without Ascaris infection to identify proteins changes potentially linked to both resistance and susceptibility amongst the two strains, respectively. Over 3000 proteins were identified in total and clear intrinsic differences were elucidated between the two strains. These included a higher abundance of mitochondrial proteins, particularly those associated with the oxidative phosphorylation pathway and reactive oxygen species (ROS) production in the relatively resistant CBA/Ca mice. We hypothesise that the increased ROS levels associated with higher levels of mitochondrial activity results in a highly oxidative cellular environment that has a dramatic effect on the nematode's ability to successfully sustain a parasitic association with its resistant host. Under infection, both strains had increased abundances in proteins ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 8 e0004837 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Gwendoline Deslyper Thomas J Colgan Andrew J R Cooper Celia V Holland James C Carolan A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The helminth Ascaris causes ascariasis in both humans and pigs. Humans, especially children, experience significant morbidity including respiratory complications, growth deficits and intestinal obstruction. Given that 800 million people worldwide are infected by Ascaris, this represents a significant global public health concern. The severity of the symptoms and associated morbidity are related to the parasite burden and not all hosts are infected equally. While the pathology of the disease has been extensively examined, our understanding of the molecular mechanisms underlying resistance and susceptibility to this nematode infection is poor. In order to investigate host differences associated with heavy and light parasite burden, an experimental murine model was developed utilising Ascaris-susceptible and -resistant mice strains, C57BL/6J and CBA/Ca, respectively, which experience differential burdens of migratory Ascaris larvae in the host lungs. Previous studies identified the liver as the site where this difference in susceptibility occurs. Using a label free quantitative proteomic approach, we analysed the hepatic proteomes of day four post infection C57BL/6J and CBA/Ca mice with and without Ascaris infection to identify proteins changes potentially linked to both resistance and susceptibility amongst the two strains, respectively. Over 3000 proteins were identified in total and clear intrinsic differences were elucidated between the two strains. These included a higher abundance of mitochondrial proteins, particularly those associated with the oxidative phosphorylation pathway and reactive oxygen species (ROS) production in the relatively resistant CBA/Ca mice. We hypothesise that the increased ROS levels associated with higher levels of mitochondrial activity results in a highly oxidative cellular environment that has a dramatic effect on the nematode's ability to successfully sustain a parasitic association with its resistant host. Under infection, both strains had increased abundances in proteins ... |
format |
Article in Journal/Newspaper |
author |
Gwendoline Deslyper Thomas J Colgan Andrew J R Cooper Celia V Holland James C Carolan |
author_facet |
Gwendoline Deslyper Thomas J Colgan Andrew J R Cooper Celia V Holland James C Carolan |
author_sort |
Gwendoline Deslyper |
title |
A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model. |
title_short |
A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model. |
title_full |
A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model. |
title_fullStr |
A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model. |
title_full_unstemmed |
A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model. |
title_sort |
proteomic investigation of hepatic resistance to ascaris in a murine model. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004837 https://doaj.org/article/2b76ff06b07a4a9ea8b02d604fa8a3a7 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 8, p e0004837 (2016) |
op_relation |
http://europepmc.org/articles/PMC4974003?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004837 https://doaj.org/article/2b76ff06b07a4a9ea8b02d604fa8a3a7 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004837 |
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PLOS Neglected Tropical Diseases |
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10 |
container_issue |
8 |
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e0004837 |
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