Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice

Jonathan Laiño, Andrea Wangorsch, Frank Blanco, Sonja Wolfheimer, Maren Krause, Adam Flaczyk, Tobias Maximilian Möller, Mindy Tsai, Stephen Galli, Stefan Vieths, Masako Toda, Stephan Scheurer, Stefan Schülke

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6 Citations (Scopus)

Abstract

Background. TLR ligands can promote Th1-biased immune responses, mimicking potent stimuli of viruses and bacteria. Aim. To investigate the adjuvant properties of dual TLR2/7 ligands compared to those of the mixture of both single ligands. Methods. Dual TLR2/7 ligands: CL401, CL413, and CL531, including CL264 (TLR7-ligand) and Pam 2 CysK 4 (TLR2-ligand), were used. Immune-modulatory capacity of the dual ligands with the individual ligands alone or as a mixture in mouse BMmDCs, BMmDC:TC cocultures, or BMCMCs was compared and assessed in naïve mice and in a mouse model of OVA-induced intestinal allergy. Results. CL413 and CL531 induced BMmDC-derived IL-10 secretion, suppressed rOVA-induced IL-5 secretion from OVA-specific DO11.10 CD4 + TCs, and induced proinflammatory cytokine secretion in vivo. In contrast, CL401 induced considerably less IL-10 secretion and led to IL-17A production in BMmDC:TC cocultures, but not BMCMC IL-6 secretion, or IL-6 or TNF-α production in vivo. No immune-modulating effects were observed with single ligands. All dual TLR2/7 ligands suppressed DNP-induced IgE-and-Ag-specific mast cell degranulation. Compared to vaccination with OVA, vaccination with the mixture CL531 and OVA, significantly suppressed OVA-specific IgE production in the intestinal allergy model. Conclusions. Based on beneficial immune-modulating properties, CL413 and CL531 may have utility as potential adjuvants for allergy treatment.

Original languageEnglish
Article number7983217
JournalJournal of immunology research
Volume2017
DOIs
Publication statusPublished - 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Laiño, J., Wangorsch, A., Blanco, F., Wolfheimer, S., Krause, M., Flaczyk, A., Möller, T. M., Tsai, M., Galli, S., Vieths, S., Toda, M., Scheurer, S., & Schülke, S. (2017). Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice. Journal of immunology research, 2017, [7983217]. https://doi.org/10.1155/2017/7983217