Trypanosoma cruzi Infection Imparts a Regulatory Program in Dendritic Cells and T Cells via Galectin-1?Dependent Mechanism

PONCINI C; ILLARREGUI J; BATALLA E; ENGELS S; CERLIANI J; CUCHER M; VAN KOOYK Y; GONZALEZ CAPPA M; RABINOVICH G

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2015

0022-1767

Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion.Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acuteparasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunityfollowing intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators,including IL-10, TGF-b1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expressionin vivo. Compared to their wild-type (WT) counterpart, Gal-1?deficient (Lgals12/2) mice exhibited reduced mortality and lowerparasite load in muscle tissue. Resistance of Lgals12/2 mice to T. cruzi infection was associated with a failure in the activation ofGal-1?driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the inductionof CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higherfrequency of IFN-g?producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden inheart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1?mediated tolerogenic circuitand reinforced T cell?dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 mayinfluence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity. The Journal of Immunology, 2015,195: 000?000.