Galectin-1 cooperates with Yersinia outer protein (Yop) P to thwart protective immunity by repressing nitric oxide produc-tion

BRENDA LUCILA JOFRE; RICARDO JAVIER ELIÇABE; JUAN EDUARDO SILVA; JUAN MANUEL PÉREZ SÁEZ; MARIA DANIELA PAEZ; EDUARDO CALLEGARI; KARINA VALERIA MARIÑO; MARÍA SILVIA DI GENARO; GABRIEL RABINOVICH; ROBERTO DAVICINO

BIOMOLECULES

MDPI

Año: 2021

2218-273X

Abstract: Yersinia enterocolitica (Ye) inserts outer proteins (Yops) into cytoplasm to infect host cells.However, in spite of considerable progress, the mechanisms implicated in thisprocess, including the association of Yops with host proteins remain unclear.Here, we evaluated the functional role of Galectin-1 (Gal1), an endogenousβ-galactoside-binding protein, in modulating Yop interactions with host cells.Our results showed that Gal1 binds to Yops in a carbohydrate-dependent manner.Interestingly, Gal1 binding to Yops protects these virulence factors fromtrypsin digestion. Given that early control of Ye infection involves activationof macrophages, we evaluated the role of Gal1 and YopP in the modulation ofmacrophage function. Although Gal1 and YopP did not influence production ofsuperoxide anion and/or TNF by Ye-infected macrophages, they coordinately inhibitednitric oxide (NO) production. Notably, recombinant Gal1 (rGal1) did not rescueNO increase observed in Lgals1-/-macrophages infected with the YopP mutant Ye ∆yopP. Whereas NO induced apoptosis inmacrophages, no significant differences in cell death were detected betweenGal1-deficient macrophages infected with Ye ∆yopP, and WT macrophages infected with Ye wt. Strikingly, increased NO production was foundin WT macrophages treated with MAPK inhibitors and infected with Ye wt.Finally, rGal1 administration did not reverse the protective effect in PeyerPatches (PPs) of Lgals1-/-mice infected with Ye ∆yopP.Our study reveals a cooperative role of YopP and endogenous Gal1 during Ye infection.