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Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events.

ABSTRACT: Plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step of malaria infection, the requirements of Plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of P. berghei-infected hepatoma cells. The data analysis shows differential expression patterns for 1064 host genes starting at 6 h and up to 24 h post infection, with the largest proportion correlating specifically with the early stages of the infection process. A considerable proportion of those genes were also found to be modulated in liver cells collected from P. yoelii-infected mice 24 and 40 h after infection, strengthening the data obtained with the in vitro model and highlighting genes and pathways involved in the host response to rodent Plasmodium parasites.Our data reveal that host cell infection by Plasmodium sporozoites leads to a coordinated and sequential set of biological events, ranging from the initial stage of stress response up to the engagement of host metabolic processes and the maintenance of cell viability throughout infection.

SUBMITTER: Albuquerque SS

PROVIDER: S-EPMC2706893 | biostudies-other | 2009 Jun

REPOSITORIES: biostudies-other

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Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events.

Albuquerque Sónia S SS Carret Céline C Grosso Ana Rita AR Tarun Alice S AS Peng Xinxia X Kappe Stefan H I SH Prudêncio Miguel M Mota Maria M MM

BMC genomics 20090617

<h4>Background</h4>Plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step of malaria infection, the requirements of Plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.<h4>Results</h4>To gain new insights into the molecular host-parasite interactions th ...[more]

PMID: 19534804

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Project description:After entering their mammalian host via the bite of an Anopheles mosquito, Plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step in malaria infection, the requirements of Plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood. To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of P. yoelii-infected hepatocytes that were collected from P. yoelii-infected mice 24 and 40 h after infection. This in vivo microarray expression was compared with the microarray analysis of in vitro infected hepatoma cells infected with closely related rodent malaria parasite P. berghei. Differential expression patterns for host genes identify genes and pathways involved in the host response to rodent Plasmodium parasites. Keywords: gene expression Total RNA from sorted liver stage (LS) infected hepatocytes were isolated from PyGFP-infected BALB/c mice as described in Tarun et al (2008). RNA from LS-infected hepatocytes were isolated at two time points post-infection (pi): 24 hr pi (LS24) and 40 hr pi (LS40). As control, RNA from hepatocytes isolated from mock-infected mice (infected with salivary gland extract) at the same time points was also isolated following the same procedure. Total RNA was then subjected to two rounds of linear amplification using the Amino Allyl Message Amp II aRNA Amplification Kit (Ambion) according to manufaturerâs directions. The quality of total and amplified RNAs were examined with the Agilent 2100 BioanalyzerTM (Agilent Technologies) and the quantity of the RNA samples was assessed using a Nanodrop ND-1000 spectrophotometer prior to microarray hybridization. For each timepoint two independent biological replicates were obtained.

Project description:BackgroundMalaria is a one of the most important infectious diseases and is caused by parasitic protozoa of the genus Plasmodium. Previously, quantitative characterization of the P. falciparum transcriptome demonstrated that the strictly controlled progression of these parasites through their intra-erythrocytic developmental cycle is accompanied by a continuous cascade of gene expression. Although such analyses have proven immensely useful, the correlations between abundance of transcripts and their cognate proteins remain poorly characterized.ResultsHere, we present a quantitative time-course analysis of relative protein abundance for schizont-stage parasites (34 to 46 hours after invasion) based on two-dimensional differential gel electrophoresis of protein samples labeled with fluorescent dyes. For this purpose we analyzed parasite samples taken at 4-hour intervals from a tightly synchronized culture and established more than 500 individual protein abundance profiles with high temporal resolution and quantitative reproducibility. Approximately half of all profiles exhibit a significant change in abundance and 12% display an expression peak during the observed 12-hour time interval. Intriguingly, identification of 54 protein spots by mass spectrometry revealed that 58% of the corresponding proteins--including actin-I, enolase, eukaryotic initiation factor (eIF)4A, eIF5A, and several heat shock proteins--are represented by more than one isoform, presumably caused by post-translational modifications, with the various isoforms of a given protein frequently showing different expression patterns. Furthermore, comparisons with transcriptome data generated from the same parasite samples reveal evidence of significant post-transcriptional gene expression regulation.ConclusionsTogether, our data indicate that both post-transcriptional and post-translational events are widespread and of presumably great biological significance during the intra-erythrocytic development of P. falciparum.

Dataset Information

Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events.

Publications

Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events.

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