Abstract

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 (TLRs) 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 interleukin-6 (IL-6; P<0.005), but not tumor necrosis factor-α (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.

Original languageEnglish (US)
Pages (from-to)67-74
Number of pages8
JournalGenes and Immunity
Volume18
Issue number2
DOIs
StatePublished - Mar 1 2017

Fingerprint

Toll-Like Receptor 6
Toll-Like Receptor 1
Dust
Cytokines
Multigene Family
Interleukin-6
Tumor Necrosis Factor-alpha
Fungal Structures
Lipopeptides
Viral Structures
Peptidoglycan
Toll-Like Receptors
Innate Immunity
Haplotypes

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

Cite this

Epistatic effect of TLR-1,-6 and-10 polymorphisms on organic dust-mediated cytokine response. / Smith, Lynette M; Weissenburger-Moser, L. A.; Heires, A. J.; Bailey, Kristina L; Romberger, Debra; LeVan, Tricia D.

In: Genes and Immunity, Vol. 18, No. 2, 01.03.2017, p. 67-74.

Research output: Contribution to journalArticle

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