Limits...
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

Heat map of Interleukins, Interferon (IFN), Transforming Growth Factor (TGF) and tumor necrosis factor (TNF) genes.All genes with names starting with IL, IFN, TGF or TNF were selected and subject to two-way hierarchical analysis. Red indicates high expression, blue low expression, and gray intermediate. Three groups of samples (I, II and III), and three clusters of genes (green, blue and yellow) are indicated. Baseline (Green labels) and Diagnosis samples (Red labels) are separated, excluding the outlier Cali 306N Baseline sample and 375S and 302S. Solid points represent Cali (N, naïve), and open circles represent Buenaventura (S, semi-immune).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526565&req=5

pntd.0003978.g005: Heat map of Interleukins, Interferon (IFN), Transforming Growth Factor (TGF) and tumor necrosis factor (TNF) genes.All genes with names starting with IL, IFN, TGF or TNF were selected and subject to two-way hierarchical analysis. Red indicates high expression, blue low expression, and gray intermediate. Three groups of samples (I, II and III), and three clusters of genes (green, blue and yellow) are indicated. Baseline (Green labels) and Diagnosis samples (Red labels) are separated, excluding the outlier Cali 306N Baseline sample and 375S and 302S. Solid points represent Cali (N, naïve), and open circles represent Buenaventura (S, semi-immune).

Mentions: Given the importance of cytokines to regulation of the immune response, we specifically analyzed the expression of many of the genes in the RNASeq dataset that are related to Interleukin (IL), interferon (IFN), tumor necrosis factor (TNF), and transforming growth factor (TGF) signaling. This analysis revealed three groups of samples, and three clusters of genes (Fig 5). Once again, the Baseline and Diagnosis samples were separated, excluding the outlier Cali 306 Baseline sample and two others, but in this case there was no clear separation relative to pre-infection malaria status. One cluster of 14 genes, including IL32 and IL8, was not differentially expressed. Another cluster of 23 genes, including the IL4R, IL6R, and IL7R and IL17R receptors, was upregulated at Baseline, particularly strongly in three volunteers (Cali 302 and Buenaventura 341 and 375). The third cluster of 19 genes, including TNF, IL1B and IL15, showed the opposite tendency, namely up-regulation at Diagnosis, particularly strongly in two samples (314 from Cali and 324 from Buenaventura). These results imply that there is strong co-regulation of the cytokine response and infection, but that this is not mediating the differential response between naïve and semi-immune individuals. This is somewhat surprising, especially given that the experience of fever was significantly different between the two populations, who might have been predicted to differ with respect to the pyrogenic cytokines IL1, IL6, IL8 and TNF.


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)

Heat map of Interleukins, Interferon (IFN), Transforming Growth Factor (TGF) and tumor necrosis factor (TNF) genes.All genes with names starting with IL, IFN, TGF or TNF were selected and subject to two-way hierarchical analysis. Red indicates high expression, blue low expression, and gray intermediate. Three groups of samples (I, II and III), and three clusters of genes (green, blue and yellow) are indicated. Baseline (Green labels) and Diagnosis samples (Red labels) are separated, excluding the outlier Cali 306N Baseline sample and 375S and 302S. Solid points represent Cali (N, naïve), and open circles represent Buenaventura (S, semi-immune).
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003978.g005: Heat map of Interleukins, Interferon (IFN), Transforming Growth Factor (TGF) and tumor necrosis factor (TNF) genes.All genes with names starting with IL, IFN, TGF or TNF were selected and subject to two-way hierarchical analysis. Red indicates high expression, blue low expression, and gray intermediate. Three groups of samples (I, II and III), and three clusters of genes (green, blue and yellow) are indicated. Baseline (Green labels) and Diagnosis samples (Red labels) are separated, excluding the outlier Cali 306N Baseline sample and 375S and 302S. Solid points represent Cali (N, naïve), and open circles represent Buenaventura (S, semi-immune).
Mentions: Given the importance of cytokines to regulation of the immune response, we specifically analyzed the expression of many of the genes in the RNASeq dataset that are related to Interleukin (IL), interferon (IFN), tumor necrosis factor (TNF), and transforming growth factor (TGF) signaling. This analysis revealed three groups of samples, and three clusters of genes (Fig 5). Once again, the Baseline and Diagnosis samples were separated, excluding the outlier Cali 306 Baseline sample and two others, but in this case there was no clear separation relative to pre-infection malaria status. One cluster of 14 genes, including IL32 and IL8, was not differentially expressed. Another cluster of 23 genes, including the IL4R, IL6R, and IL7R and IL17R receptors, was upregulated at Baseline, particularly strongly in three volunteers (Cali 302 and Buenaventura 341 and 375). The third cluster of 19 genes, including TNF, IL1B and IL15, showed the opposite tendency, namely up-regulation at Diagnosis, particularly strongly in two samples (314 from Cali and 324 from Buenaventura). These results imply that there is strong co-regulation of the cytokine response and infection, but that this is not mediating the differential response between naïve and semi-immune individuals. This is somewhat surprising, especially given that the experience of fever was significantly different between the two populations, who might have been predicted to differ with respect to the pyrogenic cytokines IL1, IL6, IL8 and TNF.

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