Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections
Abstract Background To understand how Plasmodium falciparum malaria is controlled, it is essential to elucidate the transcriptomic responses of the human host in naturally-exposed populations. Various individual studies of the human transcriptomic responses to naturally transmitted P. falciparum inf...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-022-04374-5 |
| _version_ | 1797983957767159808 |
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| author | Yan-hui Zhang Xin-zhuan Su Jian Li Jia-jian Shi Li-hua Xie |
| author_facet | Yan-hui Zhang Xin-zhuan Su Jian Li Jia-jian Shi Li-hua Xie |
| author_sort | Yan-hui Zhang |
| collection | DOAJ |
| description | Abstract Background To understand how Plasmodium falciparum malaria is controlled, it is essential to elucidate the transcriptomic responses of the human host in naturally-exposed populations. Various individual studies of the human transcriptomic responses to naturally transmitted P. falciparum infections have been reported with varying results. Multicohort gene expression analysis by aggregating data from diverse populations into a single analysis will increase the reproducibility and reliability of the results. Methods In this study, discovery cohorts GSE1124-GPL96, GSE34404, GSE117613, and validation cohort GSE35858 were obtained from the Gene Expression Omnibus. A meta-analysis using data from the multicohort studies was performed to identify the differentially expressed genes (DEGs) between malaria-infected and noninfected individuals using the MetaIntegrator R package. Subsequently, the protein–protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. Significant modules were selected, and the hub genes were identified using the CytoHubba and MCODE plug-ins. Multicohort WGCNA was conducted to find a correlation between modules and malaria infection. Furthermore, the immune cell profile of the peripheral blood in different groups was identified using ssGSEA. Results These analyses reveal that neutrophil activation, neutrophil-mediated immunity, and neutrophil degranulation are involved in the human response to natural malaria infection. However, neutrophil cell enrichment and activation were not significantly different between mild malaria and severe malaria groups. Malaria infection also downregulates host genes in ribosome synthesis and protein translation and upregulates host cell division-related genes. Furthermore, immune cell profiling analysis shows that activated dendritic cells and type 2 T helper cells are upregulated, while activated B cells, immature B cells, and monocytes are downregulated in the malaria-infected patients relative to the noninfected individuals. Significantly higher enrichment of activated dendritic cell-related genes and significantly lower enrichment of monocyte-related genes are also observed in the peripheral blood of the severe malaria group than in the mild malaria group. Conclusion These results reveal important molecular signatures of host responses to malaria infections, providing some bases for developing malaria control strategies and protective vaccines. |
| first_indexed | 2024-04-11T06:55:19Z |
| format | Article |
| id | doaj.art-164e99584bbd466a8e9fa1bc839cc2a6 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-11T06:55:19Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-164e99584bbd466a8e9fa1bc839cc2a62022-12-22T04:39:03ZengBMCMalaria Journal1475-28752022-11-0121111110.1186/s12936-022-04374-5Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infectionsYan-hui Zhang0Xin-zhuan Su1Jian Li2Jia-jian Shi3Li-hua Xie4Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of EducationLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of HealthState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen UniversityKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of EducationKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of EducationAbstract Background To understand how Plasmodium falciparum malaria is controlled, it is essential to elucidate the transcriptomic responses of the human host in naturally-exposed populations. Various individual studies of the human transcriptomic responses to naturally transmitted P. falciparum infections have been reported with varying results. Multicohort gene expression analysis by aggregating data from diverse populations into a single analysis will increase the reproducibility and reliability of the results. Methods In this study, discovery cohorts GSE1124-GPL96, GSE34404, GSE117613, and validation cohort GSE35858 were obtained from the Gene Expression Omnibus. A meta-analysis using data from the multicohort studies was performed to identify the differentially expressed genes (DEGs) between malaria-infected and noninfected individuals using the MetaIntegrator R package. Subsequently, the protein–protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. Significant modules were selected, and the hub genes were identified using the CytoHubba and MCODE plug-ins. Multicohort WGCNA was conducted to find a correlation between modules and malaria infection. Furthermore, the immune cell profile of the peripheral blood in different groups was identified using ssGSEA. Results These analyses reveal that neutrophil activation, neutrophil-mediated immunity, and neutrophil degranulation are involved in the human response to natural malaria infection. However, neutrophil cell enrichment and activation were not significantly different between mild malaria and severe malaria groups. Malaria infection also downregulates host genes in ribosome synthesis and protein translation and upregulates host cell division-related genes. Furthermore, immune cell profiling analysis shows that activated dendritic cells and type 2 T helper cells are upregulated, while activated B cells, immature B cells, and monocytes are downregulated in the malaria-infected patients relative to the noninfected individuals. Significantly higher enrichment of activated dendritic cell-related genes and significantly lower enrichment of monocyte-related genes are also observed in the peripheral blood of the severe malaria group than in the mild malaria group. Conclusion These results reveal important molecular signatures of host responses to malaria infections, providing some bases for developing malaria control strategies and protective vaccines.https://doi.org/10.1186/s12936-022-04374-5Plasmodium falciparumMulticohort transcriptome analysisNeutrophil |
| spellingShingle | Yan-hui Zhang Xin-zhuan Su Jian Li Jia-jian Shi Li-hua Xie Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections Malaria Journal Plasmodium falciparum Multicohort transcriptome analysis Neutrophil |
| title | Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections |
| title_full | Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections |
| title_fullStr | Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections |
| title_full_unstemmed | Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections |
| title_short | Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections |
| title_sort | multicohort transcriptome analysis of whole blood identifies robust human response signatures in plasmodium falciparum infections |
| topic | Plasmodium falciparum Multicohort transcriptome analysis Neutrophil |
| url | https://doi.org/10.1186/s12936-022-04374-5 |
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