Upregulation of the expression of Toll-like receptor 9 in basophils in patients with allergic rhinitis: An enhanced expression by allergens

Scand J Immunol. 2021 Mar;93(3):e13003. doi: 10.1111/sji.13003. Epub 2020 Dec 11.

Abstract

It was reported that the expression of Toll-like receptor (TLR) 9 may be related to Th2-type allergic inflammation including allergic rhinitis (AR). However, little is known about the expression of TLR9 in the basophils in AR. In the present study, the expression of TLR9 was examined by flow cytometry analysis, and the expression of TLR9 mRNA in KU812 was determined by quantitative real-time PCR. The results showed that the percentage of TLR9+ CCR3+ cells in blood granulocytes increased by 46% in patients with AR, but not in peripheral blood mononuclear cells (PBMCs). Allergens namely Dermatophagoide allergen extract (DAE) and Platanus pollen allergen extract (PPAE) upregulated the expression of TLR9 in CCR3+ granulocytes by 76% and 84%, respectively. DAE and PPAE also enhanced the proportions of TLR9+ CD123+ HLA-DR- cells and TLR9+ CCR3+ CD123+ HLA-DR- cells in granulocytes and PBMCs of patients with AR. In order to investigate the actions of allergens on basophils, KU812 cells were used. It was observed that all KU812 cells expressed TLR9, and the expression intensity of TLR9 in a single KU812 cell was elevated by CpG. IL-37, IL-31, IL-33, Artemisia sieversiana wild allergen extract (ASWAE), DAE, OVA and Der p 1 induced an increase in the expression of TLR9 mRNA and IL-6 production in KU812 cells. It was shown that the percentage of TLR9-expressing basophils increased in the blood of ovalbumin (OVA)-sensitized mice. In conclusion, an increased expression of TLR9 and the production of IL-6 in basophils implicate that the contribution of basophils to AR is likely via TLR9.

Keywords: Toll-like receptor 9; allergic rhinitis; basophil.

MeSH terms

  • Adult
  • Allergens / immunology
  • Animals
  • Basophils / metabolism*
  • Cell Line
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Granulocytes / metabolism
  • HLA-DR Antigens / immunology
  • Humans
  • Immunoglobulin E / blood
  • Interleukin-13 / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Ovalbumin / immunology
  • Pollen / immunology*
  • Pyroglyphidae / immunology*
  • RNA, Messenger / biosynthesis
  • Rhinitis, Allergic / immunology*
  • Rhinitis, Allergic / pathology
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / metabolism*
  • Up-Regulation / genetics
  • Young Adult

Substances

  • Allergens
  • HLA-DR Antigens
  • IL6 protein, human
  • Interleukin-13
  • Interleukin-6
  • RNA, Messenger
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Immunoglobulin E
  • Ovalbumin