Targeting of immune cells by dual tlr2/7 ligands suppresses features of allergic th2 immune responses in mice

  • 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 Pam2CysK4 (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.

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Author:Jonathan LaiñoORCiD, Andrea Wangorsch, Frank Eliezer Blanco PérezORCiDGND, Sonja Wolfheimer, Maren Krause, Adam FlaczykORCiD, Tobias-Maximilian Möller, Mindy Tsai, Stephen Galli, Stefan ViethsGND, Masako Toda, Stephan ScheurerORCiD, Stefan SchülkeORCiDGND
Pubmed Id:
Parent Title (English):Journal of immunology research
Place of publication:New York, NY
Contributor(s):Carol Leung
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/10/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/01/22
Issue:Art. 7983217
Page Number:13
First Page:1
Last Page:12
Copyright © 2017 Jonathan Laiño et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0