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, includ...
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doaj-df02e6017e06492ebb6440c9717829f42020-11-24T22:55:16ZengHindawi LimitedJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/79832177983217Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in MiceJonathan Laiño0Andrea Wangorsch1Frank Blanco2Sonja Wolfheimer3Maren Krause4Adam Flaczyk5Tobias-Maximilian Möller6Mindy Tsai7Stephen Galli8Stefan Vieths9Masako Toda10Stephan Scheurer11Stefan Schülke12Vice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyDepartment of Pathology and The Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, USADepartment of Pathology and The Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, USAVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyVice President’s Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, GermanyBackground. 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.http://dx.doi.org/10.1155/2017/7983217 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice Journal of Immunology Research |
author_facet |
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 |
author_sort |
Jonathan Laiño |
title |
Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice |
title_short |
Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice |
title_full |
Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice |
title_fullStr |
Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice |
title_full_unstemmed |
Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice |
title_sort |
targeting of immune cells by dual tlr2/7 ligands suppresses features of allergic th2 immune responses in mice |
publisher |
Hindawi Limited |
series |
Journal of Immunology Research |
issn |
2314-8861 2314-7156 |
publishDate |
2017-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2017/7983217 |
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