Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group
Canadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examin...
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ftpubmed:oai:pubmedcentral.nih.gov:6775093 2023-05-15T16:16:59+02:00 Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group Semple, Catlin Choi, Ka-Yee Grace Kroeker, Andrea Denechezhe, Lizette Orr, Pamela Mookherjee, Neeloffer Larcombe, Linda 2019-10-02 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775093/ http://www.ncbi.nlm.nih.gov/pubmed/31578370 https://doi.org/10.1038/s41598-019-50596-0 en eng Nature Publishing Group UK http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775093/ http://www.ncbi.nlm.nih.gov/pubmed/31578370 http://dx.doi.org/10.1038/s41598-019-50596-0 © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. CC-BY Article Text 2019 ftpubmed https://doi.org/10.1038/s41598-019-50596-0 2019-10-13T00:20:48Z Canadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examined the production of a panel of 30 cytokines in peripheral blood-derived mononuclear cells (PBMC) isolated from Indigenous and non-Indigenous participants, following stimulation with five different TLR ligands. The levels of TLR-induced pro-inflammatory cytokines such as IL-12/23p40, IL-16, and IFN-γ, and chemokines (MCP-4, MDC and eotaxin) were different between Indigenous compared to non-Indigenous participants. Antimicrobial cationic host defence peptides (CHDP) induced by TLR activation are critical for resolution of infections and modulate the TLR-to-NFκB pathway to alter downstream cytokine responses. Therefore, we examined the expression of human CHDP defensins and cathelicidin in PBMC. mRNA expression of genes encoding for def-A1 and def-B1 were significantly higher following stimulation with TLR ligands in Indigenous compared to non-Indigenous participants. The purinergic receptor P2X7 known to be activated by ATP released following TLR stimulation, is a receptor for CHDP. Therefore, we further examined single nucleotide polymorphisms (SNP) in P2X7. Indigenous participants had a significantly higher percentage of a P2X7 SNP which is associated with reduced function and lower ability to clear infections. These results suggest that a higher frequency of non-functional P2X7 receptors may influence the activity of downstream immune mediators required for resolution of infections such as pro-inflammatory cytokines and CHDP defensins, thus contributing to higher burden of infections in Indigenous population. Text First Nations inuit PubMed Central (PMC) Scientific Reports 9 1 |
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Article Semple, Catlin Choi, Ka-Yee Grace Kroeker, Andrea Denechezhe, Lizette Orr, Pamela Mookherjee, Neeloffer Larcombe, Linda Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group |
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Canadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examined the production of a panel of 30 cytokines in peripheral blood-derived mononuclear cells (PBMC) isolated from Indigenous and non-Indigenous participants, following stimulation with five different TLR ligands. The levels of TLR-induced pro-inflammatory cytokines such as IL-12/23p40, IL-16, and IFN-γ, and chemokines (MCP-4, MDC and eotaxin) were different between Indigenous compared to non-Indigenous participants. Antimicrobial cationic host defence peptides (CHDP) induced by TLR activation are critical for resolution of infections and modulate the TLR-to-NFκB pathway to alter downstream cytokine responses. Therefore, we examined the expression of human CHDP defensins and cathelicidin in PBMC. mRNA expression of genes encoding for def-A1 and def-B1 were significantly higher following stimulation with TLR ligands in Indigenous compared to non-Indigenous participants. The purinergic receptor P2X7 known to be activated by ATP released following TLR stimulation, is a receptor for CHDP. Therefore, we further examined single nucleotide polymorphisms (SNP) in P2X7. Indigenous participants had a significantly higher percentage of a P2X7 SNP which is associated with reduced function and lower ability to clear infections. These results suggest that a higher frequency of non-functional P2X7 receptors may influence the activity of downstream immune mediators required for resolution of infections such as pro-inflammatory cytokines and CHDP defensins, thus contributing to higher burden of infections in Indigenous population. |
format |
Text |
author |
Semple, Catlin Choi, Ka-Yee Grace Kroeker, Andrea Denechezhe, Lizette Orr, Pamela Mookherjee, Neeloffer Larcombe, Linda |
author_facet |
Semple, Catlin Choi, Ka-Yee Grace Kroeker, Andrea Denechezhe, Lizette Orr, Pamela Mookherjee, Neeloffer Larcombe, Linda |
author_sort |
Semple, Catlin |
title |
Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group |
title_short |
Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group |
title_full |
Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group |
title_fullStr |
Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group |
title_full_unstemmed |
Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group |
title_sort |
polymorphisms in the p2x7 receptor, and differential expression of toll-like receptor-mediated cytokines and defensins, in a canadian indigenous group |
publisher |
Nature Publishing Group UK |
publishDate |
2019 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775093/ http://www.ncbi.nlm.nih.gov/pubmed/31578370 https://doi.org/10.1038/s41598-019-50596-0 |
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First Nations inuit |
genre_facet |
First Nations inuit |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775093/ http://www.ncbi.nlm.nih.gov/pubmed/31578370 http://dx.doi.org/10.1038/s41598-019-50596-0 |
op_rights |
© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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CC-BY |
op_doi |
https://doi.org/10.1038/s41598-019-50596-0 |
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Scientific Reports |
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