Galectin-8 stimulates a protective immune response in a viral infection model

CARABELLI, JULIETA; PRATO, CECILIA ARAHÍ; VALERIA QUATTROCCHI; ALEJANDRA D'ANTUONO; PATRICIA ZAMORANO; TRIBULATTI MARÍA VIRGINIA; CAMPETELLA, OSCAR

CANNES

Workshop; EMBO Workshop on Transducing glycan information into function: Lessons from galectins.; 2016

EMBO

Galectin-8 is a mammalian lectin, endowed with pro-inflammatory properties. We have previously shown that Gal-8 is able to elicit antigen-specific CD4 T cell response in the transgenic DO11.10TCROVA model, both in vitroand in vivo. Here, we further tested the stimulating capacity of Gal-8 in the elicitation of an effective immune response using an experimental foot and mouth disease virus (FMDV) model. For this purpose, soluble rGal-8 was co-administrated with antigen during immunization of BALB/cJ mice with the inactivated virus (iFMDV). The use of a single dose of recombinant Gal-8 (rGal-8) in antigen formulation increased an specific and neutralizing humoral response, sufficient to enhance animal protection upon viral challenge. The response of rGal-8/iFMDV-immunized animals was also characterized by increased levels of IL-6 and INF-γ, as well as lymphoproliferation. These latter results were only observed at early times after immunization (48h), suggesting that Gal-8 participates in the elicitation of the adaptive immune response. In order to get a deeper insight in the mechanism by which Gal-8 stimulates the antigen-specific immune response, we investigated whether Gal-8 was able to promote antigen-presenting cells activation to sustain T cell activation after priming. Bone marrow-derived dendritic cells (DC) treated with exogenous rGal-8 exhibited a mature phenotype characterized by increased expression of the co-stimulatory molecules MHC II, CD80 and CD86 and the secretion of pro-inflammatory cytokines (IL-3, IL-2, IL-6, TNF-α, MCP-1 and MPC-5), and growth factor G-CSF. Of note, IL-6 was the most abundant cytokine induced in Gal-8-treated DC conditioned media. Remarkably, Gal-8-activated DC stimulated antigen-specific CD4 T cells more efficiently than their immature counterparts. Finally, the presence of Gal-8 increased antigen uptake by immature DC. Taking together, these findings strongly suggest that Gal-8 activates antigen-presenting cells to elicit a protective immune response, and argue in favour of the use of Gal-8 as an immune-stimulator molecule.