Regulated expression of galectins 1 and 3 IS associated with dysregulated T cell responses in pulmonary and pleural tuberculosis

Abstract

Galectins exert a wide range of effects on immune cells in acute and chronic pathologies, although their effects are less described in chronic infections such as tuberculosis-TB. We assessed galectin-1 (Gal-1) and galectin-3 (Gal-3) concentrations and immune mediators in plasma from pulmonary TB-PTB cases (n=38), healthy controls-Hco (n=24), and patients with pleural TB-PLTB (n=11) in which pleural fluid-PLF was also evaluated. Galectin transcripts expression, together with glycosyltransferases, that positively (MGAT5, GCNT1) or negatively (ST6GAL1) control galectins activity, were assessed in mononuclear cells (MC). We also evaluated Gal-1 production, along with other immune-mediators, in Mtb-stimulated MCs. Both patient groups presented elevated circulating levels of pro- and anti-inflammatory mediators and reduced cell proliferation, but a marked T-cell response at the pleural compartment. PTB patients had increased Gal-1 in levels in plasma and higher Gal-1 mRNA levels in MCs (p<0.01, vs. Hco). Both TB groups showed high plasma Gal-3 concentrations and increased expression in MCs (p<0.01 vs. HCo). PLF showed the lowest levels of both galectins, as did their expressions on MCs from pleural effusion. Only PBMCs from PTB exhibited increased expression of GCNT1 (p<0.04) together with diminished ST6GAL1 suggesting enhanced availability of galectin ligands. Mtb-stimulated MCs from both patient groups showed increased Gal-1 production compared to HCo. Moreover, unstimulated cultures from PTB presented a major basal production of Gal-1. Thus, a balance of circulating levels of galectins, pro- and anti-inflammatory mediators, and the differential expression of these lectins as well as glycosylation-related enzymes in MCs, may condition cell function particularly in PTB cases.