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

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
journal of photochemistry and photobiology b, biology 2017 Vol. 2017 pp. -
537
laio2017journaltargeting

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 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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134446
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10.1155/2017/7983217
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