Targeting of immune cells by dual TLR2/7 ligands suppresses features of allergic TH2 immune responses in mice.

JONATHAN LAIÑO; ANDREA WANGORSCH; FRANK BLANCO PEREZ; SONJA WOLFHEIMER; MAREN KRAUSE; ADAM FALCZYK; MINDY TSAI; S. GALLI; STEFAN VIETHS; MASAKO TODA; STEPHAN SCHEURER; TOBIAS-MAXIMILIAN MÖLLER; STEFAN SCHÜLKE

Journal of Immunology Research

Hindawi

Lugar: Londres; Año: 2017 vol. 2017 p. 1 - 12

2314-8861

Background: When combined, different TLR-ligands can act in addition or synergy to promote Th1-biased immune responses while mimicking potent immune stimuli of viruses and bacteria. Aim: To investigate the adjuvant properties of conjugated dual TLR2/7-ligands compared to the mixture of both TLR-ligands. Methods: We evaluated three different dual TLR2/7-ligands: CL401, CL413, and CL531, all incorporating the immune stimulatory TLR7-ligand, 9-benzyl-8-hydroxyadenine CL264, and the TLR2-ligand, Pam2CysK4. We compared the immune modulatory capacity of the dual ligands to equimolar amounts of the individual ligands used alone or as a mixture by testing mouse BMmDCs, BMmDC:TC co-cultures, BMCMCs and by assessing their immune activating potential in naïve mice and in a mouse model of OVA-induced intestinal allergy. Results: CL413 and CL531 induced BMmDC 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, led to IL-17A production in BMmDC:TC co-cultures, and failed to induce either C57BL/6 BMCMC IL-6 secretion or IL-6 or TNF-a production in vivo. Interestingly, these immune modulating effects were not observed when applying the TLR2- and TLR7-ligands alone or as a mixture. Of note, all dual TLR2/7-ligands suppressed DNP-induced, IgE-and-Ag-specific mast cell degranulation upon coapplication with DNP-HSA. Compared to prophylactic vaccination with OVA, vaccination with the mixture of CL531 and OVA, but not with the component TLR2 and TLR7 ligands alone, significantly suppressed OVA-specific IgE production in a mouse model of OVA-induced intestinal allergy. Conclusions: Because of their beneficial immune modulating properties, we suggest that CL413 and CL531 may have utility as potential adjuvants for allergy treatment.