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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

Experimental design.The time line sample collection, 85 total samples for RT-qPCR analysis and 24 total samples for RNASeq. Green arrows represent timepoints where RT-qPCR Pre-challenge, 16 samples (7 Cali, 9 Buenaventura); Day 5, 14 samples (6 Cali, 8 Buenaventura); Day 7, 14 samples (5 Cali, 9 Buenaventura); Day 9, 16 (7 Cali, 9 Buenaventura); Diagnosis by tick blood smear day (Day 12–13), 11 samples (5 Cali, 6 Buenaventura) and Month 4, 15 samples (6 Cali, 9 Buenaventura). Blue arrows shows samples used for the RNASeq analysis 12 per each timepoint Diagnosis day and Pre-challenge (6 Cali, 6 Buenaventura) 24 total.
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pntd.0003978.g001: Experimental design.The time line sample collection, 85 total samples for RT-qPCR analysis and 24 total samples for RNASeq. Green arrows represent timepoints where RT-qPCR Pre-challenge, 16 samples (7 Cali, 9 Buenaventura); Day 5, 14 samples (6 Cali, 8 Buenaventura); Day 7, 14 samples (5 Cali, 9 Buenaventura); Day 9, 16 (7 Cali, 9 Buenaventura); Diagnosis by tick blood smear day (Day 12–13), 11 samples (5 Cali, 6 Buenaventura) and Month 4, 15 samples (6 Cali, 9 Buenaventura). Blue arrows shows samples used for the RNASeq analysis 12 per each timepoint Diagnosis day and Pre-challenge (6 Cali, 6 Buenaventura) 24 total.

Mentions: Volunteers where invited to the vaccine center two days (day -2) prior the challenge day (day 0) for physical examination and blood sample collection. Fig 1 summarizes the blood sampling strategy. Blood samples used for the RT-qPCR experiment were collected on day -2 (pre-challenge), day 5, day 7, day 9, on the day of first detection of Plasmodium by thick smear test (day 12–13), and on month 4. RNASeq analysis, also approved by the Georgia Tech IRB, was performed for 12 individuals (six each from Buenaventura and Cali) for two of the timepoints, namely the diagnosis day and baseline (pre-challenge day).


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)

Experimental design.The time line sample collection, 85 total samples for RT-qPCR analysis and 24 total samples for RNASeq. Green arrows represent timepoints where RT-qPCR Pre-challenge, 16 samples (7 Cali, 9 Buenaventura); Day 5, 14 samples (6 Cali, 8 Buenaventura); Day 7, 14 samples (5 Cali, 9 Buenaventura); Day 9, 16 (7 Cali, 9 Buenaventura); Diagnosis by tick blood smear day (Day 12–13), 11 samples (5 Cali, 6 Buenaventura) and Month 4, 15 samples (6 Cali, 9 Buenaventura). Blue arrows shows samples used for the RNASeq analysis 12 per each timepoint Diagnosis day and Pre-challenge (6 Cali, 6 Buenaventura) 24 total.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003978.g001: Experimental design.The time line sample collection, 85 total samples for RT-qPCR analysis and 24 total samples for RNASeq. Green arrows represent timepoints where RT-qPCR Pre-challenge, 16 samples (7 Cali, 9 Buenaventura); Day 5, 14 samples (6 Cali, 8 Buenaventura); Day 7, 14 samples (5 Cali, 9 Buenaventura); Day 9, 16 (7 Cali, 9 Buenaventura); Diagnosis by tick blood smear day (Day 12–13), 11 samples (5 Cali, 6 Buenaventura) and Month 4, 15 samples (6 Cali, 9 Buenaventura). Blue arrows shows samples used for the RNASeq analysis 12 per each timepoint Diagnosis day and Pre-challenge (6 Cali, 6 Buenaventura) 24 total.
Mentions: Volunteers where invited to the vaccine center two days (day -2) prior the challenge day (day 0) for physical examination and blood sample collection. Fig 1 summarizes the blood sampling strategy. Blood samples used for the RT-qPCR experiment were collected on day -2 (pre-challenge), day 5, day 7, day 9, on the day of first detection of Plasmodium by thick smear test (day 12–13), and on month 4. RNASeq analysis, also approved by the Georgia Tech IRB, was performed for 12 individuals (six each from Buenaventura and Cali) for two of the timepoints, namely the diagnosis day and baseline (pre-challenge day).

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