Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria
Abstract Background To date all efforts to develop a malaria vaccine have failed, reflecting the still fragmentary knowledge about protective mechanisms against malaria. In order to evaluate if vaccination changes responses of the anti-malaria effectors spleen and liver to blood stage malaria, BALB/...
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ftdoajarticles:oai:doaj.org/article:b9b948af7c0d426fbfe0ef8defa6d05e 2023-05-15T15:13:15+02:00 Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria Dkhil Mohamed A El-Khadragy Manal Wojtalla Anna Pauen Heike Delić Denis Krücken Jürgen Mossmann Horst Wunderlich Frank 2009-04-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-54 https://doaj.org/article/b9b948af7c0d426fbfe0ef8defa6d05e EN eng BMC http://www.malariajournal.com/content/8/1/54 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-54 1475-2875 https://doaj.org/article/b9b948af7c0d426fbfe0ef8defa6d05e Malaria Journal, Vol 8, Iss 1, p 54 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-54 2022-12-31T01:53:57Z Abstract Background To date all efforts to develop a malaria vaccine have failed, reflecting the still fragmentary knowledge about protective mechanisms against malaria. In order to evaluate if vaccination changes responses of the anti-malaria effectors spleen and liver to blood stage malaria, BALB/c mice succumbing to infection with Plasmodium chabaudi were compared to those surviving after vaccination. Methods Mice were vaccinated with host cell plasma membranes isolated from P. chabaudi -infected erythrocytes. Hepatic and splenic capacity to trap particulate material was determined after injection of fluorescent polystyrol beads. Hepatic gene expression was measured using real-time RT-PCR and Northern blotting. Results Survival of BALB/c mice was raised from 0% to 80% and peak parasitaemia was decreased by about 30% by vaccination. Vaccination boosted particle trapping capacity of the liver during crisis when splenic trapping is minimal due to spleen 'closing'. It also attenuated malaria-induced inflammation, thus diminishing severe damages and hence liver failure. Vaccination increased hepatic IFN-γ production but mitigated acute phase response. Vaccination has a complex influence on infection-induced changes in expression of hepatic nuclear receptors (CAR, FXR, RXR, and PXR) and of the metabolic enzymes Sult2a and Cyp7a1. Although vaccination decreased CAR mRNA levels and prevented Cyp7a1 suppression by the CAR ligand 1,2-bis [2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) on day 8 p.i., Sult2a-induction by TCPOBOP was restored. Conclusion These data support the view that the liver is an essential effector site for a vaccine against blood stage malaria: vaccination attenuates malaria-induced inflammation thus improving hepatic metabolic activity and particle trapping activity of the liver. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 8 1 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Dkhil Mohamed A El-Khadragy Manal Wojtalla Anna Pauen Heike Delić Denis Krücken Jürgen Mossmann Horst Wunderlich Frank Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background To date all efforts to develop a malaria vaccine have failed, reflecting the still fragmentary knowledge about protective mechanisms against malaria. In order to evaluate if vaccination changes responses of the anti-malaria effectors spleen and liver to blood stage malaria, BALB/c mice succumbing to infection with Plasmodium chabaudi were compared to those surviving after vaccination. Methods Mice were vaccinated with host cell plasma membranes isolated from P. chabaudi -infected erythrocytes. Hepatic and splenic capacity to trap particulate material was determined after injection of fluorescent polystyrol beads. Hepatic gene expression was measured using real-time RT-PCR and Northern blotting. Results Survival of BALB/c mice was raised from 0% to 80% and peak parasitaemia was decreased by about 30% by vaccination. Vaccination boosted particle trapping capacity of the liver during crisis when splenic trapping is minimal due to spleen 'closing'. It also attenuated malaria-induced inflammation, thus diminishing severe damages and hence liver failure. Vaccination increased hepatic IFN-γ production but mitigated acute phase response. Vaccination has a complex influence on infection-induced changes in expression of hepatic nuclear receptors (CAR, FXR, RXR, and PXR) and of the metabolic enzymes Sult2a and Cyp7a1. Although vaccination decreased CAR mRNA levels and prevented Cyp7a1 suppression by the CAR ligand 1,2-bis [2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) on day 8 p.i., Sult2a-induction by TCPOBOP was restored. Conclusion These data support the view that the liver is an essential effector site for a vaccine against blood stage malaria: vaccination attenuates malaria-induced inflammation thus improving hepatic metabolic activity and particle trapping activity of the liver. |
format |
Article in Journal/Newspaper |
author |
Dkhil Mohamed A El-Khadragy Manal Wojtalla Anna Pauen Heike Delić Denis Krücken Jürgen Mossmann Horst Wunderlich Frank |
author_facet |
Dkhil Mohamed A El-Khadragy Manal Wojtalla Anna Pauen Heike Delić Denis Krücken Jürgen Mossmann Horst Wunderlich Frank |
author_sort |
Dkhil Mohamed A |
title |
Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria |
title_short |
Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria |
title_full |
Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria |
title_fullStr |
Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria |
title_full_unstemmed |
Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria |
title_sort |
augmented particle trapping and attenuated inflammation in the liver by protective vaccination against plasmodium chabaudi malaria |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-54 https://doaj.org/article/b9b948af7c0d426fbfe0ef8defa6d05e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 54 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/54 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-54 1475-2875 https://doaj.org/article/b9b948af7c0d426fbfe0ef8defa6d05e |
op_doi |
https://doi.org/10.1186/1475-2875-8-54 |
container_title |
Malaria Journal |
container_volume |
8 |
container_issue |
1 |
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1766343825177968640 |