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Transcription Profiling of Malaria-Naïve and Semi-immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge.

Rojas-Peña ML, Vallejo A, Herrera S, Gibson G, Arévalo-Herrera M - PLoS Negl Trop Dis (2015)

Bottom Line: There was no evidence for transcriptional changes prior to the appearance of blood stage parasites at day 12 or 13, at which time there was a strong interferon response and, unexpectedly, down-regulation of transcripts related to inflammation and innate immunity.This differential expression was confirmed with RNASeq, which also suggested perturbations of aspects of T cell function and erythropoiesis.Despite differences in clinical symptoms between the semi-immune and malaria naïve individuals, only subtle differences in their transcriptomes were observed, although 175 genes showed significantly greater induction or repression in the naïve volunteers from Cali.

View Article: PubMed Central - PubMed

Affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Continued exposure to malaria-causing parasites in endemic regions of malaria induces significant levels of acquired immunity in adult individuals. A better understanding of the transcriptional basis for this acquired immunological response may provide insight into how the immune system can be boosted during vaccination, and into why infected individuals differ in symptomology.

Methodology/principal findings: Peripheral blood gene expression profiles of 9 semi-immune volunteers from a Plasmodium vivax malaria prevalent region (Buenaventura, Colombia) were compared to those of 7 naïve individuals from a region with no reported transmission of malaria (Cali, Colombia) after a controlled infection mosquito bite challenge with P. vivax. A Fluidigm nanoscale quantitative RT-PCR array was used to survey altered expression of 96 blood informative transcripts at 7 timepoints after controlled infection, and RNASeq was used to contrast pre-infection and early parasitemia timepoints. There was no evidence for transcriptional changes prior to the appearance of blood stage parasites at day 12 or 13, at which time there was a strong interferon response and, unexpectedly, down-regulation of transcripts related to inflammation and innate immunity. This differential expression was confirmed with RNASeq, which also suggested perturbations of aspects of T cell function and erythropoiesis. Despite differences in clinical symptoms between the semi-immune and malaria naïve individuals, only subtle differences in their transcriptomes were observed, although 175 genes showed significantly greater induction or repression in the naïve volunteers from Cali.

Conclusion/significance: Gene expression profiling of whole blood reveals the type and duration of the immune response to P. vivax infection, and highlights a subset of genes that may mediate adaptive immunity.

No MeSH data available.


Related in: MedlinePlus

Principal component variance component analyses.Bar graphs shows the weighted average of the variance captured by the first five principal components among samples that is explained by Time (PRE, DAY5, DAY7, DAY9, Diagnosis, MTH4), Site (Cali, Buenaventura) and individual, indicating that most the variability is among individual for RT-qPCR (A) and Time (PRE and Diagnosis day) for RNASeq data set (B).
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pntd.0003978.g002: Principal component variance component analyses.Bar graphs shows the weighted average of the variance captured by the first five principal components among samples that is explained by Time (PRE, DAY5, DAY7, DAY9, Diagnosis, MTH4), Site (Cali, Buenaventura) and individual, indicating that most the variability is among individual for RT-qPCR (A) and Time (PRE and Diagnosis day) for RNASeq data set (B).

Mentions: Whole blood gene expression was monitored in each of the 85 samples using a Fluidigm nanoscale RT-qPCR array targeting 96 genes referred as “blood informative transcripts” (BIT) (S5 Table). These BIT consistently capture the covariance of over half of the genes expressed in blood, specifically serving as biomarkers for 10 conserved axes of variation. Across all of the gene expression measurements, 30% of the variance was among individuals, and just 6.5% between the timepoints, with very little differentiation between the naïve and pre-immune volunteers (Fig 2). The remainder of the variance was due to random biological or technical noise, or to the covariance of gene expression along the Axes.


Transcription Profiling of Malaria-Naïve and Semi-immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge.

Rojas-Peña ML, Vallejo A, Herrera S, Gibson G, Arévalo-Herrera M - PLoS Negl Trop Dis (2015)

Principal component variance component analyses.Bar graphs shows the weighted average of the variance captured by the first five principal components among samples that is explained by Time (PRE, DAY5, DAY7, DAY9, Diagnosis, MTH4), Site (Cali, Buenaventura) and individual, indicating that most the variability is among individual for RT-qPCR (A) and Time (PRE and Diagnosis day) for RNASeq data set (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526565&req=5

pntd.0003978.g002: Principal component variance component analyses.Bar graphs shows the weighted average of the variance captured by the first five principal components among samples that is explained by Time (PRE, DAY5, DAY7, DAY9, Diagnosis, MTH4), Site (Cali, Buenaventura) and individual, indicating that most the variability is among individual for RT-qPCR (A) and Time (PRE and Diagnosis day) for RNASeq data set (B).
Mentions: Whole blood gene expression was monitored in each of the 85 samples using a Fluidigm nanoscale RT-qPCR array targeting 96 genes referred as “blood informative transcripts” (BIT) (S5 Table). These BIT consistently capture the covariance of over half of the genes expressed in blood, specifically serving as biomarkers for 10 conserved axes of variation. Across all of the gene expression measurements, 30% of the variance was among individuals, and just 6.5% between the timepoints, with very little differentiation between the naïve and pre-immune volunteers (Fig 2). The remainder of the variance was due to random biological or technical noise, or to the covariance of gene expression along the Axes.

Bottom Line: There was no evidence for transcriptional changes prior to the appearance of blood stage parasites at day 12 or 13, at which time there was a strong interferon response and, unexpectedly, down-regulation of transcripts related to inflammation and innate immunity.This differential expression was confirmed with RNASeq, which also suggested perturbations of aspects of T cell function and erythropoiesis.Despite differences in clinical symptoms between the semi-immune and malaria naïve individuals, only subtle differences in their transcriptomes were observed, although 175 genes showed significantly greater induction or repression in the naïve volunteers from Cali.

View Article: PubMed Central - PubMed

Affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Continued exposure to malaria-causing parasites in endemic regions of malaria induces significant levels of acquired immunity in adult individuals. A better understanding of the transcriptional basis for this acquired immunological response may provide insight into how the immune system can be boosted during vaccination, and into why infected individuals differ in symptomology.

Methodology/principal findings: Peripheral blood gene expression profiles of 9 semi-immune volunteers from a Plasmodium vivax malaria prevalent region (Buenaventura, Colombia) were compared to those of 7 naïve individuals from a region with no reported transmission of malaria (Cali, Colombia) after a controlled infection mosquito bite challenge with P. vivax. A Fluidigm nanoscale quantitative RT-PCR array was used to survey altered expression of 96 blood informative transcripts at 7 timepoints after controlled infection, and RNASeq was used to contrast pre-infection and early parasitemia timepoints. There was no evidence for transcriptional changes prior to the appearance of blood stage parasites at day 12 or 13, at which time there was a strong interferon response and, unexpectedly, down-regulation of transcripts related to inflammation and innate immunity. This differential expression was confirmed with RNASeq, which also suggested perturbations of aspects of T cell function and erythropoiesis. Despite differences in clinical symptoms between the semi-immune and malaria naïve individuals, only subtle differences in their transcriptomes were observed, although 175 genes showed significantly greater induction or repression in the naïve volunteers from Cali.

Conclusion/significance: Gene expression profiling of whole blood reveals the type and duration of the immune response to P. vivax infection, and highlights a subset of genes that may mediate adaptive immunity.

No MeSH data available.


Related in: MedlinePlus