Gene expression of liver of vaccination-protected mice in response to early patent infections of Plasmodium chabaudi blood-stage malaria
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PROVIDER: PRJNA435948 | ENA |
REPOSITORIES: ENA
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Project description:The role of the liver for survival of blood-stage malaria is only fragmentary understood. In the experimental blood-stage malaria Plasmodium chabaudi, protective vaccination induces self-healing and, thus, survival of otherwise lethal infections. This study investigates the response of the liver, in terms of mRNA and lincRNA expression, to vaccination-induced self-healing infections and lethal P. chabaudi malaria at early patency on day 4 p.i., when parasitized erythrocytes begin to appear in peripheral blood. Using gene expression microarrays, 23 genes were identified to be induced in the liver by >10-fold at p<0.01. More than one third were genes involved in erythropoiesis, as e.g. Kel, Rhag, Ahsp, Ermap, Slc4a1, Cldn13 Gata1, and Gfi1b. Another group of >10-fold expressed genes contain genes involved in natural cytotoxicity, as those encoding the killer cell lectin-like like receptors Klrb1a, Klrc3, Klrd1, Ncr1 and the granzyme B encoding Gzmb. In addition, there were identified a series of genes involved in the control of cell cycle and mitosis, as Ccnb1, Cdc25c, Ckap2l expressed by >10-fold only in vaccination-protected mice, and 22 genes being at least 100% higher expressed in vaccination-protected mice than the corresponding genes significantly expressed in non-vaccinated mice. Furthermore, distinct lincRNA species were changed by >3-fold in livers of vaccination-protected mice, whereas lethal malaria induced different lincRNAs. Our data suggest that protective vaccination accelerates extramedullary erythropoiesis, generation of liver-resident cytotoxic cells, and regeneration from malaria-induced injuries in the liver at early patency, which may be critical for final survival of otherwise lethal blood-stage malaria of P. chabaudi. Mice: Balb/c mice breeded under specified pathogen-free conditions were delivered from central animal facilities of the University of Düsseldorf. The experiments were performed only with female mice aged 10-12 weeks. They were housed in plastic cages, received a standard diet (Woehrlin, Bad Salzuflen, Germany) and water ad libitum. This study was carried out in strict accordance with the German law on animal protection. The keeping of mice as well as the experimental protocol of the study were officially approved by the State-controlled Committee on the Ethics of Animal Experiments of the State Nordrhein-Westfalen, Germany, and were regularly controlled, without being previously announced, by the local authorities. All efforts were undertaken to minimize suffering of mice. P. chabaudi malaria infection: Blood-stage infections of P. chabaudi were kept in outbred mice under sterile conditions by weekly passages of infected blood. A non-clonal line of P. chabaudi is used in our laboratory since 1982, which resembles to P. chabaudi chabaudi. Challenge of Balb/c mice with 10^6 P. chabaudi-infected erythrocytes, Protective vaccination: As a vaccine, host cell plasma membranes were used, which were isolated in the form of ghosts from P. chabaudi-parasitized erythrocytes Approximately 10^6 ghosts were suspended in 100 µl Freund’s complete adjuvant (FCA) and subcutaneously injected on week 3 and week 1 before infecting with P. chabaudi-parasitized erythrocytes. Control mice were treated in parallel only FCA.
2018-06-06 | GSE111110 | GEO
Project description:Increasing evidence suggests the liver as to be an effector against blood-stage malaria. Vaccination induces changes in the liver and survival of otherwise lethal blood-stage malaria of Plasmodium chabaudi which is associated with changes in the liver. Here, the time-course of expression of erythroid genes is investigated during infections with P. chabaudi in the liver of vaccination-protected and unprotected non-vaccinated mice.
2020-02-10 | GSE129133 | GEO
Project description:Protective vaccination induces survival of more than 80% of female Balb/c mice otherwise succumbing to blood-stage malaria of Plasmodium chabaudi. This study investigates the effect of protective vaccination and P. chabaudi infections on DNA methylation of gene promoters in the liver of Balb/c mice. Using DNA methylation microarrays, protective vaccination is shown to affect per se the constitutive DNA methylation status of numerous gene promoters in the liver: Promoters of 256 genes are hyper(=up)- and 345 genes are hypo (=down)-methylated at a significance of p<0.05. Gene enrichment analysis reveals that genes with down-methylated promoters are most statistically significant enriched (p<0.01) with functions related to negative regulation of transcription, whereas genes with up-methylated promoters are related to positive regulation of transcription and immune system. Infections with P. chabaudi also induce changes in promoter DNA methylation. In vaccinated mice, these changes are observable already on day 1 p.i. and, in particular, at peak parasitemia on day 8 p.i., when 571 and 1013 gene promoters have become up- and down-methylated, respectively, in relation to constitutive DNA methylation at a signicance level of p<0.05. The corresponding gene promoters in non-vaccinated mice are also responsive to infection, but by far not as pronounced as in vaccinated mice. Our data demonstrate that vaccination modifies DNA methylation of gene promoters in the liver and augments promoter responsiveness to infection-induced DNA methylation alterations, which ultimately control expression of those genes in the liver required for survival of otherwise lethal blood-stage malaria of P. chabaudi.
2019-09-23 | GSE87373 | GEO
Project description:The aim of the present study was to analyze the effect of protective vaccination on the miRNome of the liver during the crisis phase in vaccination-induced self-healing infections of Plasmodium chabaudi in comparison to lethal infections in non-protected Balb/c mice using Agilentâs microRNA expression microarrays.
2017-04-01 | E-MTAB-5301 | biostudies-arrayexpress
Project description:The aim of the present study was to analyze the effect of protective vaccination on the transcriptome of the liver towards the end of the crisis phase in vaccination-induced self-healing infections of Plasmodium chabaudi in comparison to lethal infections in non-protected Balb/c mice using Agilentâs gene expression microarrays.
2016-10-01 | E-MTAB-4791 | biostudies-arrayexpress
Project description:RTS,S is the sole candidate vaccine shown to provide protection against infection to malaria-naive adults challenged with mosquito-borne homologous falciparum malaria and protection against infection and clinical and severe disease to volunteers in malaria-endemic Africa who were exposed to diverse Plasmodium falciparum strains. In this experiment we profiled gene expression in PBMCs after vaccination with the RTS,S candidate malaria vaccine in a controlled human malaria infection study. Subjects were vaccinated with three doses of the RTS,S candidate malaria vaccine. Blood samples for PBMC isolation and subsequent gene expression analysis were taken on day 0 (0m), day of the third vaccination (8w), 1 day post third vaccination (8w1d), 3 days post third vaccination (8w3d), the day of the infection (10w), 1 day post infection (10w1d), and 5 days post infection (10w5d). After infection the subjects were closely monitored for parasitemia. The response to the controlled infection was recorded as follows: no parasitemia (P, protected), parasitemia in the same time frame as the control group (NP, not protected), parasitemia later than the control group (DL, delayed). In addition to the experimental factors, a confounding factor was identified in the data analysis related to the use of a specific kit batch (Kit A or B).
2017-04-27 | E-MTAB-4629 | biostudies-arrayexpress
Project description:Identification of gene signatures that are associated with protection in RTS,S malaria vaccination study
2020-04-21 | GSE102288 | GEO
Project description:The purpose of this research is to identify and evaluate the global gene expression of the rodent malaria parasites Plasmodium yoelii, Plasmodium berghei and Plasmodium chabaudi blood-stage parasites and specifically compare the blood stage gene expression profiles of samples derived from previous studies on Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi
2016-04-08 | GSE80015 | GEO
Project description:Analysis of blood samples taken throughout the acute phase of infection from mice infected with avirulent P. chabaudi AS strain or virulent CB strain The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for lung inflammation, stronger and prolonged anemia and platelet aggregation. The latter two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria infections shows the validity of this approach to inform severity of malarial infection and provide insight into pathogenic mechanisms.
2017-02-01 | GSE93631 | GEO
Project description:Identification of host responses that are induced by RTS,S vaccination in controlled malaria infection
2020-04-21 | GSE107672 | GEO