Galectin-8 activates dendritic cells and stimulates antigen-specific immune response elicitation.
Carabelli, J., Quattrocchi, V., D’Antuono, A., Zamorano, P., Tribulatti, M.V. and Campetella, O.
Laboratorio de Inmunologia Molecular, Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico de Chascomus, Universidad Nacional de San Martin, Consejo Nacional de Investigaciones Cientificas y Tecnicas, San Martin, Buenos Aires, Argentina.
Instituto de Virologia, Instituto Nacional de Tecnologia Agropecuario, Castelar, Buenos Aires, Argentina; and.
Centro de Virologia Animal, Instituto de Ciencias y Tecnologia "Dr. Cesar Milstein," Ciudad Autonoma de Buenos Aires, Argentina.
Laboratorio de Inmunologia Molecular, Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico de Chascomus, Universidad Nacional de San Martin, Consejo Nacional de Investigaciones Cientificas y Tecnicas, San Martin, Buenos Aires, Argentina; virginiatribu@gmail.com.
Galectin-8 (Gal-8) is a mammalian beta-galactoside-binding lectin, endowed with proinflammatory properties. Given its capacity to enhance antigen-specific immune responses in vivo, we investigated whether Gal-8 was also able to promote APC activation to sustain T cell activation after priming. Both endogenous [dendritic cells (DCs)] and bone marrow-derived DCs (BMDCs) treated with exogenous Gal-8 exhibited a mature phenotype characterized by increased MHC class II (MHCII), CD80, and CD86 surface expression. Moreover, Gal-8-treated BMDCs (Gal-8-BMDCs) stimulated antigen-specific T cells more efficiently than immature BMDCs (iBMDCs). Proinflammatory cytokines IL-3, IL-2, IL-6, TNF, MCP-1, and MCP-5, as well as growth factor G-CSF, were augmented in Gal-8-BMDC conditioned media, with IL-6 as the most prominent. Remarkably, BMDCs from Gal-8-deficient mice (Lgals8-/- BMDC) displayed reduced CD86 and IL-6 expression and an impaired ability to promote antigen-specific CD4 T cell activation. 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 (FMDV) 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-gamma, as well as lymphoproliferative responses, were also incremented in Gal-8/antigen-immunized animals only at 48 h 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.
Journal of Leukocyte Biology : en prensa (2017)