Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice
| Autor: | Adam Flaczyk, Stefan Vieths, Stephan Scheurer, Jonathan Emiliano Laiño, Stephen J. Galli, Andrea Wangorsch, Frank Blanco, Tobias Maximilian Möller, Stefan Schülke, Sonja Wolfheimer, Mindy Tsai, Maren Krause, Masako Toda |
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| Přispěvatelé: | Leung, Carol |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Article Subject medicine.medical_treatment Immunology Mice Transgenic Immunoglobulin E Lymphocyte Activation Proinflammatory cytokine Immunomodulation 03 medical and health sciences Lipopeptides Mice 0302 clinical medicine Immune system Th2 Cells In vivo medicine Hypersensitivity Immunology and Allergy Animals Humans Secretion Molecular Targeted Therapy ddc:610 Cells Cultured Mice Inbred BALB C Membrane Glycoproteins biology Degranulation General Medicine Dendritic Cells Th1 Cells Coculture Techniques Toll-Like Receptor 2 Mice Inbred C57BL TLR2 030104 developmental biology Toll-Like Receptor 7 biology.protein lcsh:RC581-607 Adjuvant 030215 immunology Research Article |
| Zdroj: | Journal of Immunology Research, Vol 2017 (2017) Journal of Immunology Research |
| ISSN: | 2314-8861 |
| DOI: | 10.1155/2017/7983217 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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