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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

Log2 Parasitemia and Axis 2 and 5 Benin Study, West Africa.Significant correlation is evident between parasitemia and axis of variation, even though unrelated to location. A. Axis 5, r = 0.20, p = 0.0079. B. Axis 1, r = -0.47, p = 1.4×10-9. Neither interaction effect is significant, indicating that the correlation is similar in both locations. Each plot shows the correlation between location and axis of variation, blue represents samples from Cotonou, red represents samples from Zinvié; solid points represent control and open circles represent malaria samples.
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pntd.0003978.g007: Log2 Parasitemia and Axis 2 and 5 Benin Study, West Africa.Significant correlation is evident between parasitemia and axis of variation, even though unrelated to location. A. Axis 5, r = 0.20, p = 0.0079. B. Axis 1, r = -0.47, p = 1.4×10-9. Neither interaction effect is significant, indicating that the correlation is similar in both locations. Each plot shows the correlation between location and axis of variation, blue represents samples from Cotonou, red represents samples from Zinvié; solid points represent control and open circles represent malaria samples.

Mentions: Finally, we reanalyzed an infant malarial gene expression dataset from Benin [9]. All samples were collected within a period of 10 weeks in the Spring of 2010, and transcript abundance data was generated on Illumina HumanHT-12 BeadChips for 155 individuals (61 controls from Cotonou, 24 high parasitemia from the village of Zinvie, 52 low parasitemia from Zinvie, and 18 from the city of Cotonou). Critical differences relative to our study include (i) comparison with P. falciparum rather than with P. vivax infection, (ii) infants versus young adults comparison, and (iii) cross-sectional rather than Baseline vs Diagnosis analysis. Nevertheless, a significant correlation (Fig 7A and 7B) was observed between parasitemia and two Axes of variation, Axes 1 and 5. However, in this case there was activation of the innate immunity/inflammation genes as parasite burden increases. Axis 1, which is enriched for T-cell signaling activity [15], was strongly reduced as parasitemia increased, but like Axis 5, not significantly affected in the infants with low parasitemia. From 32 genes showing a significant interaction effect between timepoint and population in our challenge experiment, 12 were nominally differentially expressed between malaria patients in the city of Cotonou and rural village of Zinvie in Benin.


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)

Log2 Parasitemia and Axis 2 and 5 Benin Study, West Africa.Significant correlation is evident between parasitemia and axis of variation, even though unrelated to location. A. Axis 5, r = 0.20, p = 0.0079. B. Axis 1, r = -0.47, p = 1.4×10-9. Neither interaction effect is significant, indicating that the correlation is similar in both locations. Each plot shows the correlation between location and axis of variation, blue represents samples from Cotonou, red represents samples from Zinvié; solid points represent control and open circles represent malaria samples.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003978.g007: Log2 Parasitemia and Axis 2 and 5 Benin Study, West Africa.Significant correlation is evident between parasitemia and axis of variation, even though unrelated to location. A. Axis 5, r = 0.20, p = 0.0079. B. Axis 1, r = -0.47, p = 1.4×10-9. Neither interaction effect is significant, indicating that the correlation is similar in both locations. Each plot shows the correlation between location and axis of variation, blue represents samples from Cotonou, red represents samples from Zinvié; solid points represent control and open circles represent malaria samples.
Mentions: Finally, we reanalyzed an infant malarial gene expression dataset from Benin [9]. All samples were collected within a period of 10 weeks in the Spring of 2010, and transcript abundance data was generated on Illumina HumanHT-12 BeadChips for 155 individuals (61 controls from Cotonou, 24 high parasitemia from the village of Zinvie, 52 low parasitemia from Zinvie, and 18 from the city of Cotonou). Critical differences relative to our study include (i) comparison with P. falciparum rather than with P. vivax infection, (ii) infants versus young adults comparison, and (iii) cross-sectional rather than Baseline vs Diagnosis analysis. Nevertheless, a significant correlation (Fig 7A and 7B) was observed between parasitemia and two Axes of variation, Axes 1 and 5. However, in this case there was activation of the innate immunity/inflammation genes as parasite burden increases. Axis 1, which is enriched for T-cell signaling activity [15], was strongly reduced as parasitemia increased, but like Axis 5, not significantly affected in the infants with low parasitemia. From 32 genes showing a significant interaction effect between timepoint and population in our challenge experiment, 12 were nominally differentially expressed between malaria patients in the city of Cotonou and rural village of Zinvie in Benin.

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