Dataset Information

Transcription Profiling of Malaria-Naïve and Semi-Immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge [RNA-Seq]

ABSTRACT: We report two clusters in the overall profiles of expression among the samples. At the parasitemia onset, there is a strong interferon response reflected in up-regulation of co-regulated transcripts, while unexpectedly we also see down-regulation of transcripts related to TLR signaling and innate immunity. RNASeq also suggested differential expression of reticulocytes and a subset of T cell function. No obvious difference in the transcriptomes of naïve and semi-immune volunteers was seen, however several hundred genes were up-regulated in naïve individuals.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67184 | GEO | 2015/07/14

SECONDARY ACCESSION(S): PRJNA279199

REPOSITORIES: GEO

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Project description:Microarray studies using synchronized Plasmodium falciparum parasites have revealed a ‘continuous cascade’ of gene expression. Reports vary regarding the stability in these transcriptional patterns in the presence of external stressors. Using Plasmodium yoelii 17X parasites replicating in vivo, we have examined differential gene expression in parasites isolated from individual mice, from independent infections, during ascending and peak parasitemia and in the presence and absence of host antibody responses. Across experimental conditions, transcription was surprisingly stable. Differential gene expression was greatest when comparing differences due to parasite load and/or host cell availability; however, even these changes were modest. Of genes that were differentially expressed, many are of unknown function. There was little to no differential expression of members of the yir and pyst-a multigene families, although a relatively large number of these were expressed during blood-stage infection regardless of experimental condition. Taken together, these results indicate that 1) P. yoelii gene expression remains stable in the presence of a changing host environment and 2) concurrent expression of a large number of the yir and pyst-a genes may function to divert host immune responses away from invariant protective antigens. 1. P. yoelii 17X gene expression profiles were determined in blood-stage parasites isolated from infected Balb/c mice (male, 8-12 weeks old) as follows: a. Mouse 1 (M1), Mouse 2 (M2), Mouse 3 (M3), Donor (D) mouse – three mice simultaneously infected with P. yoelii 17X iRBCs from a single donor mouse. Parasite RNA was isolated early during infection when parasitemia was ascending as follows: M1 - day 11 at 13.0% parasitemia; M2 - day 10 at 11.1% parasitemia; M3 - day 10 at 18.6% parasitemia; D – day 11 at 18.7% parasitemia. b. Infection #1 (I1), infection #2 (I2), infection #3 (I3), infection #4 (I4) – four groups of mice infected on four separate occasions using P. yoelii 17X iRBCs obtained from four separate donor mice. In each case, P. yoelii 17X RNA was isolated from iRBCs obtained on days 10-11 of infection when parasitemia was ascending and was ~15%. c. Day 10 (D10), Day 14 (D14) – P. yoelii 17X RNA isolated from iRBCs during infection #2 on day 10 (14% parasitemia, 14.4% reticulocytes) and on day 14 of infection #2 (43.5% parasitemia, 57.9% reticulocytes). d. WT and JHD - P. yoelii 17X RNA isolated from iRBCs during infection #4 from immunologically intact, wild-type Balb/c mice and B cell deficient, JHD mice on a Balb/c background (ascending infection, 15% parasitemia). e. QA and RMP - P. yoelii 17X RNA isolated from iRBCs during infection #1 from mice previously immunized with a preparation of membrane proteins isolated from P. yoelii 17X infected reticulocytes (PyRMP) (day 12, 13.3% parasitemia and Quil A immunized (QA) control mice (day 10, 15.6% parasitemia) 2. On each array, gene expression in P. yoelii 17X blood-stage parasites was evaluated relative to a standard comparator of purified P. yoelii 17XL total RNA (pooled RNA from 45 mice, mean parasitemia ~35%). Each sample was analyzed on three replicate arrays, one of which was a standard dye-flip. One exception was the infection #3 sample which was analyzed on only on two arrays. On each array, oligonucleotides were spotted in duplicate. 3. Through the use of the standard reference RNA, the following 15 pairwise comparisons across samples were made: (M1 vs M2); (M2 vs M3); (M1 vs M3); (D vs M1); (D vs M2); (D vs M3); (I1 vs I2); (I1 vs I3); (I1 vs I4); (I2 vs I3); (I2 vs I4); (I3 vs I4); (D10 vs D14); (WT vs JHD); (QA vs RMP)

Project description:Project Description: The Malaria Host-Pathogen Interaction Center (MaHPIC) is a transdisciplinary malaria systems biology research program initially supported by an NIH/NIAID contract (HHSN272201200031C, 2012-2017; see <a href='http://www.systemsbiology.emory.edu' target='_blank'>http://www.systemsbiology.emory.edu</a>). The MaHPIC continues with ongoing support from the Defense Advanced Research Project Agency (DARPA) and others. The MaHPIC generates many data types (e.g., clinical, hematological, parasitological, metabolomics, functional genomics, lipidomics, proteomics, immune response, telemetry) and mathematical models, to iteratively test and develop hypotheses related to the complex host-parasite dynamics in the course of malaria in non-human primates (NHPs), and metabolomics data via collaborations with investigators conducting clinical studies in malaria endemic countries, with the overarching goal of better understanding human disease, pathogenesis, and immunity. Curation and maintenance of all data and metadata are the responsibility of the MaHPIC. MaHPIC Experiment Description: Sixteen healthy volunteers, 7 malaria naïve and 9 semi-immune, aged 18-45 years, were enrolled in this study during October 2012 to November 2013. Malaria-naive volunteers were recruited in Cali, Colombia, a non-endemic city; those with previous malaria experience were recruited in Buenaventura, a malaria-endemic area on the Colombian Pacific Coast. The study was approved by Institutional Review Boards (IRB) of the Malaria Vaccine and Drug Development Center–MVDC (CECIV, Cali) and Centro Médico Imbanaco (Cali). All protocols and documentation were reviewed and samples shipments approved by the Emory IRB. Male and female patients were eligible for inclusion, which included two steps: 1) age between 15-60 years, hemoglobin levels > 9g/dL, presence of current Plasmodium vivax infection, absence of other Plasmodium species determined by thick blood smear and PCR, blood parasite count of 0.1% or more, absence of other acute or chronic diseases, being able to sign an informed consent form; 2) healthy 18 to 45 years old man or non-pregnant women, capacity to sign an informed consent in a free and voluntary way, acceptable understanding of the clinical trial through the approval of a questionnaire regarding the information given in the consent process, obligatory use of adequate contraceptive method from beginning of recruitment and screening time up to three months after last immunization, do not have chronic or acute diseases, accept not traveling to malaria endemic areas during the clinical trial, have telephone at home or mobile phone that permit permanent contact for follow up, being willing to participated during both steps of the clinical trial. Exclusion criteria included pregnancy, abnormal laboratory test values, hemoglobin pathology, glucose-6-phosphate dehydrogenase (G6PDH) deficiency, positive for blood bank infectious diseases (syphilis, HIV, Chagas disease, HTLV 1–2, and hepatitis B and hepatitis C), or have any condition that would increase the risk of an adverse outcome. Volunteers were infected with P. vivax via sporozoite challenge by exposing volunteers to bites of 2–4 mosquitoes (Anopheles albimanus) of the same infected batch. Plasma samples were collected at 4 time points: Baseline, 1 month pre-inoculation; Diagnosis; 3 weeks post-treatment; 4 months post-treatment. As soon as parasites were detected by thick blood smears, participants were treated orally with curative doses of chloroquine (1500 mg chloroquine provided in three doses: 600 mg initially then 450 mg doses at 24 and 48 hours) and primaquine (30 mg dose given once per day for 14 days). Clinical trial registration: NCT01585077. Samples were analyzed with liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS), evaluated in a time course and between naïve and semi-immune volunteers. Within the MaHPIC, this project is known as ‘Experiment HuC’. Samples were obtained in collaboration with Socrates Herrera from the Malaria Vaccine and Drug Development Center, Colombia. Metabolomics results were produced by Dean Jones at Emory University. To access other publicly available results from HuC and other MaHPIC Experiments visit <a href='http://plasmodb.org/plasmo/mahpic.jsp' target='_blank'>http://plasmodb.org/plasmo/mahpic.jsp</a> . This page will be updated as datasets are released to the public. The following contributed to the creation of this dataset: The MaHPIC Consortium, Jeremy D. DeBarry, Mary R. Galinski, Luiz G. Gardinassi, Socrates Herrera, Myriam Arévalo-Herrera, Dean P. Jones, Jessica C. Kissinger, Shuzhao Li, Regina Joice Cordy, Esmeralda VS Meyer, Mustafa V. Nural, Suman B. Pakala, ViLinh Tran, Karan Uppal Linked Studies: <a href='/metabolights/search?freeTextQuery=MaHPIC' target='_blank'>Malaria Host-Pathogen Interaction Center (MaHPIC)</a>

Dataset Information

Transcription Profiling of Malaria-Naïve and Semi-Immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge [RNA-Seq]

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