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Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response

Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of toll-like receptors and drive host innate and adaptive resp...

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Autores principales: Smith, Lynette M., Weissenburger-Moser, Lisa A., Heires, Art J., Bailey, Kristina L., Romberger, Debra J., LeVan, Tricia D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407948/
https://www.ncbi.nlm.nih.gov/pubmed/28123183
http://dx.doi.org/10.1038/gene.2016.51
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author Smith, Lynette M.
Weissenburger-Moser, Lisa A.
Heires, Art J.
Bailey, Kristina L.
Romberger, Debra J.
LeVan, Tricia D.
author_facet Smith, Lynette M.
Weissenburger-Moser, Lisa A.
Heires, Art J.
Bailey, Kristina L.
Romberger, Debra J.
LeVan, Tricia D.
author_sort Smith, Lynette M.
collection PubMed
description Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of toll-like receptors and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)(4) (Pam3CSK4) and the diacyl- lipopeptide peptidoglycan. Several of the tagging polymorphisms and haplotypes conferred hyper-responsiveness to organic dust with an increase in IL-6 (p < 0.005), but not TNF-α, secretion. We conclude that genetic variation in the TLR10-TLR1-TLR6 gene cluster mediates responsiveness to organic dust, but indicates different signaling pathways for IL-6 and TNF-α. These studies provide new insight into the role of the TLR10-TLR1-TLR6 gene cluster and the innate immune response to organic dust.
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spelling pubmed-54079482017-09-01 Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response Smith, Lynette M. Weissenburger-Moser, Lisa A. Heires, Art J. Bailey, Kristina L. Romberger, Debra J. LeVan, Tricia D. Genes Immun Article Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of toll-like receptors and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)(4) (Pam3CSK4) and the diacyl- lipopeptide peptidoglycan. Several of the tagging polymorphisms and haplotypes conferred hyper-responsiveness to organic dust with an increase in IL-6 (p < 0.005), but not TNF-α, secretion. We conclude that genetic variation in the TLR10-TLR1-TLR6 gene cluster mediates responsiveness to organic dust, but indicates different signaling pathways for IL-6 and TNF-α. These studies provide new insight into the role of the TLR10-TLR1-TLR6 gene cluster and the innate immune response to organic dust. 2017-01-26 2017-03 /pmc/articles/PMC5407948/ /pubmed/28123183 http://dx.doi.org/10.1038/gene.2016.51 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Smith, Lynette M.
Weissenburger-Moser, Lisa A.
Heires, Art J.
Bailey, Kristina L.
Romberger, Debra J.
LeVan, Tricia D.
Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response
title Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response
title_full Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response
title_fullStr Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response
title_full_unstemmed Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response
title_short Epistatic effect of TLR −1, −6 and −10 Polymorphisms on Organic Dust-Mediated Cytokine Response
title_sort epistatic effect of tlr −1, −6 and −10 polymorphisms on organic dust-mediated cytokine response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407948/
https://www.ncbi.nlm.nih.gov/pubmed/28123183
http://dx.doi.org/10.1038/gene.2016.51
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