Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation
The proper control of Plasmodium infection requires a finely balanced immune response. Here, we evaluated the implication of TGF-β1 and TGF-β3 in this process using novel monoclonal antibodies to measure their plasma concentrations in comparison with other cytokines and the expression of FOXP3 mRNA....
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12665 |
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| author | Ella Larissa Ndoricyimpaye Jacques Van Snick Jean de Dieu Niyoyita Philbert Kanimba Jean Bosco Mbonimpa Robert Rutayisire Réverien Rutayisire Vedaste Ndahindwa Paméla Cheou Jean Paul Coutelier Nadine Rujeni |
| author_facet | Ella Larissa Ndoricyimpaye Jacques Van Snick Jean de Dieu Niyoyita Philbert Kanimba Jean Bosco Mbonimpa Robert Rutayisire Réverien Rutayisire Vedaste Ndahindwa Paméla Cheou Jean Paul Coutelier Nadine Rujeni |
| author_sort | Ella Larissa Ndoricyimpaye |
| collection | DOAJ |
| description | The proper control of Plasmodium infection requires a finely balanced immune response. Here, we evaluated the implication of TGF-β1 and TGF-β3 in this process using novel monoclonal antibodies to measure their plasma concentrations in comparison with other cytokines and the expression of FOXP3 mRNA. Plasma cytokine levels were measured in 80 patients with severe anaemic malaria and 186 with a mild presentation using ELISA, and rtPCR was used to measure FOXP3 mRNA expression. While no mature TGF-β isoforms were detected in the plasma, the latent TGF-β1 and TGF-β3 were strongly upregulated in patients with mild malaria and nearly undetected in patients with severe disease. Similar selective upregulation in mild patients was observed for IL-9 and FOXP3 mRNA, while IL-7, IL-10, IL-17, and IL-27, although higher in mild cases, were also detected in severe disease. In contrast, a clearly skewed trend of severe cases towards higher pro-inflammatory (IL-6, IL-13, TNF-α) and Th1 (IFN-γ) responses was observed, which was associated with a higher level of parasitaemia as well as lower IgG and higher IgM responses. Together, these results suggest that the stimulation of regulatory T cells through TGF-β1/TGF-β3 and IL-9 is paramount to an effective and balanced protective immunity in natural human malaria infection. |
| first_indexed | 2024-03-09T20:05:20Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:05:20Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ea78ee459f5b4dc49da131a0803c5d8b2023-11-24T00:35:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201266510.3390/ijms232012665Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical PresentationElla Larissa Ndoricyimpaye0Jacques Van Snick1Jean de Dieu Niyoyita2Philbert Kanimba3Jean Bosco Mbonimpa4Robert Rutayisire5Réverien Rutayisire6Vedaste Ndahindwa7Paméla Cheou8Jean Paul Coutelier9Nadine Rujeni10Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaLudwig Institute for Cancer Research, Université Catholique de Louvain, 1348 Brussels, BelgiumBiomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaBiomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaBiomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaBiomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaBiomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaSchool of Public Health, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaMedecine Expérimentale, de Duve Institute, Université Catholique de Louvain, 1348 Brussels, BelgiumBiomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaBiomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, RwandaThe proper control of Plasmodium infection requires a finely balanced immune response. Here, we evaluated the implication of TGF-β1 and TGF-β3 in this process using novel monoclonal antibodies to measure their plasma concentrations in comparison with other cytokines and the expression of FOXP3 mRNA. Plasma cytokine levels were measured in 80 patients with severe anaemic malaria and 186 with a mild presentation using ELISA, and rtPCR was used to measure FOXP3 mRNA expression. While no mature TGF-β isoforms were detected in the plasma, the latent TGF-β1 and TGF-β3 were strongly upregulated in patients with mild malaria and nearly undetected in patients with severe disease. Similar selective upregulation in mild patients was observed for IL-9 and FOXP3 mRNA, while IL-7, IL-10, IL-17, and IL-27, although higher in mild cases, were also detected in severe disease. In contrast, a clearly skewed trend of severe cases towards higher pro-inflammatory (IL-6, IL-13, TNF-α) and Th1 (IFN-γ) responses was observed, which was associated with a higher level of parasitaemia as well as lower IgG and higher IgM responses. Together, these results suggest that the stimulation of regulatory T cells through TGF-β1/TGF-β3 and IL-9 is paramount to an effective and balanced protective immunity in natural human malaria infection.https://www.mdpi.com/1422-0067/23/20/12665malaria patternpro-inflammatory cytokinesparasiteregulatory cytokinesTregs |
| spellingShingle | Ella Larissa Ndoricyimpaye Jacques Van Snick Jean de Dieu Niyoyita Philbert Kanimba Jean Bosco Mbonimpa Robert Rutayisire Réverien Rutayisire Vedaste Ndahindwa Paméla Cheou Jean Paul Coutelier Nadine Rujeni Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation International Journal of Molecular Sciences malaria pattern pro-inflammatory cytokines parasite regulatory cytokines Tregs |
| title | Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation |
| title_full | Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation |
| title_fullStr | Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation |
| title_full_unstemmed | Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation |
| title_short | Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation |
| title_sort | integrated analysis of cytokine profiles in malaria patients discloses selective upregulation of tgf β1 β3 and il 9 in mild clinical presentation |
| topic | malaria pattern pro-inflammatory cytokines parasite regulatory cytokines Tregs |
| url | https://www.mdpi.com/1422-0067/23/20/12665 |
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