Galectin-8 activates dendritic cells and stimulates antigen-specific immune response elicitation

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

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2017 vol. 102 p. 1237 - 1247

0741-5400

Galectin-8 (Gal-8) is a mammalian beta-galactoside-binding lectin, endowed with pro-inflammatory properties. Given its capacity to enhance antigen-specific immune responses in vivo, we investigated whether Gal-8 was also able to promote antigen-presenting cells activation to sustain T cell activation after priming. Both endogenous (DC) and bone marrow-derived (BMDC) dendritic cells treated with exogenous Gal-8 exhibited a mature phenotype characterized by increased MHCII, CD80 and CD86 surface expression. Moreover, Gal-8-treated BMDC stimulated antigen-specific T cells more efficiently than immature BMDC. Pro-inflammatory cytokines IL-3, IL-2, IL-6, TNF, MCP-1 and MPC-5, as well as growth factor G-CSF, were augmented in Gal-8-treated BMDC conditioned media, being IL-6 the most prominent. Remarkably, BMDC from Gal-8-deficient mice (Lgal8-/-37 BMDC) displayed reduced CD86 and IL-6 expression, and an impaired ability to promote antigen-specific CD4 T cell activation. In order to test if Gal-8-induced activation correlates with the elicitation of an effective immune response, soluble Gal-8 was coadministrated with antigen during immunization of BALB/cJ mice in the experimental Foot-and-Mouth Disease Virus model. When a single dose of Gal-8 was added to the antigen formulation, an increased specific and neutralizing humoral response was developed, sufficient to enhance animal protection upon viral challenge. IL-6 and IFN-γ as well as lymphoproliferative responses were also incremented in Gal-8/antigen immunized animals only at 48h after immunization, suggesting that Gal-8 induces the elicitation of an inflammatory response at an early stage. Taking together, these findings argue in favor of the use of Gal-8 as an immune-stimulator molecule to enhance the adaptive immune response.