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Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study
BACKGROUND: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infec...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784286/ https://www.ncbi.nlm.nih.gov/pubmed/26961973 http://dx.doi.org/10.1186/s12936-016-1189-6 |
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author | Sobota, Rafal S. Dara, Antoine Manning, Jessica E. Niangaly, Amadou Bailey, Jason A. Kone, Abdoulaye K. Thera, Mahamadou A. Djimdé, Abdoulaye A. Vernet, Guy Leissner, Philippe Williams, Scott M. Plowe, Christopher V. Doumbo, Ogobara K. |
author_facet | Sobota, Rafal S. Dara, Antoine Manning, Jessica E. Niangaly, Amadou Bailey, Jason A. Kone, Abdoulaye K. Thera, Mahamadou A. Djimdé, Abdoulaye A. Vernet, Guy Leissner, Philippe Williams, Scott M. Plowe, Christopher V. Doumbo, Ogobara K. |
author_sort | Sobota, Rafal S. |
collection | PubMed |
description | BACKGROUND: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood. METHODS: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression data on severe cases and uncomplicated controls at the time of acute disease presentation (five uncomplicated and five severe), 1 week after presentation (three uncomplicated and three severe) and treatment initiation, and in the subsequent dry season (late convalescence, four uncomplicated and four severe). This is a pilot study for the first use of microarray technology in Mali. RESULTS: Complement and toll-like receptor (TLR) pathways were differentially expressed, with severe cases showing higher expression of the C1q, TLR2, TLR4, TLR8, and CR1 genes. Other genes previously associated with malaria pathogenesis, GZMB, FOS and HSPA6, were also higher among severe cases. TLR2, TLR4, TLR8, CR1, GZMB, FOS, and HSPA6 genes were expressed at lower levels in severe cases at late convalescence. CONCLUSIONS: Overexpression of genes previously associated with uncomplicated malaria was associated with severe disease. Low baseline expression of these genes may represent candidate markers for severe malaria. Despite the small sample size, results of this pilot study offer promising targets for follow-up analyses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-016-1189-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4784286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47842862016-03-10 Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study Sobota, Rafal S. Dara, Antoine Manning, Jessica E. Niangaly, Amadou Bailey, Jason A. Kone, Abdoulaye K. Thera, Mahamadou A. Djimdé, Abdoulaye A. Vernet, Guy Leissner, Philippe Williams, Scott M. Plowe, Christopher V. Doumbo, Ogobara K. Malar J Research BACKGROUND: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood. METHODS: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression data on severe cases and uncomplicated controls at the time of acute disease presentation (five uncomplicated and five severe), 1 week after presentation (three uncomplicated and three severe) and treatment initiation, and in the subsequent dry season (late convalescence, four uncomplicated and four severe). This is a pilot study for the first use of microarray technology in Mali. RESULTS: Complement and toll-like receptor (TLR) pathways were differentially expressed, with severe cases showing higher expression of the C1q, TLR2, TLR4, TLR8, and CR1 genes. Other genes previously associated with malaria pathogenesis, GZMB, FOS and HSPA6, were also higher among severe cases. TLR2, TLR4, TLR8, CR1, GZMB, FOS, and HSPA6 genes were expressed at lower levels in severe cases at late convalescence. CONCLUSIONS: Overexpression of genes previously associated with uncomplicated malaria was associated with severe disease. Low baseline expression of these genes may represent candidate markers for severe malaria. Despite the small sample size, results of this pilot study offer promising targets for follow-up analyses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-016-1189-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-09 /pmc/articles/PMC4784286/ /pubmed/26961973 http://dx.doi.org/10.1186/s12936-016-1189-6 Text en © Sobota et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Sobota, Rafal S. Dara, Antoine Manning, Jessica E. Niangaly, Amadou Bailey, Jason A. Kone, Abdoulaye K. Thera, Mahamadou A. Djimdé, Abdoulaye A. Vernet, Guy Leissner, Philippe Williams, Scott M. Plowe, Christopher V. Doumbo, Ogobara K. Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study |
title | Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study |
title_full | Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study |
title_fullStr | Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study |
title_full_unstemmed | Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study |
title_short | Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study |
title_sort | expression of complement and toll-like receptor pathway genes is associated with malaria severity in mali: a pilot case control study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784286/ https://www.ncbi.nlm.nih.gov/pubmed/26961973 http://dx.doi.org/10.1186/s12936-016-1189-6 |
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