Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.

Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria. While many intracellular pathogens subvert the MHC class I presentation machinery, its functionality in the course of malaria replication in hep...

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Autores principales:	Jinxia Ma, Stefanie Trop, Samantha Baer, Elian Rakhmanaliev, Zita Arany, Peter Dumoulin, Hao Zhang, Julia Romano, Isabelle Coppens, Victor Levitsky, Jelena Levitskaya
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e09d1355f11a4c29833e9b05d5fca36d
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spelling	oai:doaj.org-article:e09d1355f11a4c29833e9b05d5fca36d2021-11-18T08:53:47ZDynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.1932-620310.1371/journal.pone.0075321https://doaj.org/article/e09d1355f11a4c29833e9b05d5fca36d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086507/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria. While many intracellular pathogens subvert the MHC class I presentation machinery, its functionality in the course of malaria replication in hepatocytes has not been characterized. Using experimental systems based on specific identification, isolation and analysis of human hepatocytes infected with P. berghei ANKA GFP or P. falciparum 3D7 GFP sporozoites we demonstrated that molecular components of the MHC class I pathway exhibit largely unaltered expression in malaria-infected hepatocytes until very late stages of parasite development. Furthermore, infected cells showed no obvious defects in their capacity to upregulate expression of different molecular components of the MHC class I machinery in response to pro-inflammatory lymphokines or trigger direct activation of allo-specific or peptide-specific human CD8+ T-cells. We further demonstrate that ectopic expression of circumsporozoite protein does not alter expression of critical genes of the MHC class I pathway and its response to pro-inflammatory cytokines. In addition, we identified supra-cellular structures, which arose at late stages of parasite replication, possessed the characteristic morphology of merosomes and exhibited nearly complete loss of surface MHC class I expression. These data have multiple implications for our understanding of natural T-cell immunity against malaria and may promote development of novel, efficient anti-malaria vaccines overcoming immune escape of the parasite in the liver.Jinxia MaStefanie TropSamantha BaerElian RakhmanalievZita AranyPeter DumoulinHao ZhangJulia RomanoIsabelle CoppensVictor LevitskyJelena LevitskayaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75321 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jinxia Ma Stefanie Trop Samantha Baer Elian Rakhmanaliev Zita Arany Peter Dumoulin Hao Zhang Julia Romano Isabelle Coppens Victor Levitsky Jelena Levitskaya Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
description	Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria. While many intracellular pathogens subvert the MHC class I presentation machinery, its functionality in the course of malaria replication in hepatocytes has not been characterized. Using experimental systems based on specific identification, isolation and analysis of human hepatocytes infected with P. berghei ANKA GFP or P. falciparum 3D7 GFP sporozoites we demonstrated that molecular components of the MHC class I pathway exhibit largely unaltered expression in malaria-infected hepatocytes until very late stages of parasite development. Furthermore, infected cells showed no obvious defects in their capacity to upregulate expression of different molecular components of the MHC class I machinery in response to pro-inflammatory lymphokines or trigger direct activation of allo-specific or peptide-specific human CD8+ T-cells. We further demonstrate that ectopic expression of circumsporozoite protein does not alter expression of critical genes of the MHC class I pathway and its response to pro-inflammatory cytokines. In addition, we identified supra-cellular structures, which arose at late stages of parasite replication, possessed the characteristic morphology of merosomes and exhibited nearly complete loss of surface MHC class I expression. These data have multiple implications for our understanding of natural T-cell immunity against malaria and may promote development of novel, efficient anti-malaria vaccines overcoming immune escape of the parasite in the liver.
format	article
author	Jinxia Ma Stefanie Trop Samantha Baer Elian Rakhmanaliev Zita Arany Peter Dumoulin Hao Zhang Julia Romano Isabelle Coppens Victor Levitsky Jelena Levitskaya
author_facet	Jinxia Ma Stefanie Trop Samantha Baer Elian Rakhmanaliev Zita Arany Peter Dumoulin Hao Zhang Julia Romano Isabelle Coppens Victor Levitsky Jelena Levitskaya
author_sort	Jinxia Ma
title	Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
title_short	Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
title_full	Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
title_fullStr	Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
title_full_unstemmed	Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
title_sort	dynamics of the major histocompatibility complex class i processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e09d1355f11a4c29833e9b05d5fca36d
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Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.

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