Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production

<i>Yersinia enterocolitica</i> (Ye) inserts outer proteins (Yops) into cytoplasm to infect host cells. However, in spite of considerable progress, the mechanisms implicated in this process, including the association of Yops with host proteins, remain unclear. Here, we evaluated the funct...

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Autores principales:	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 Adrián Rabinovich, Roberto Carlos Davicino
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Yersinia enterocolitica</i> YopP Galectin-1 nitric oxide macrophages Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7f938e391dbe46baa1741ebfbb0ddd88
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spelling	oai:doaj.org-article:7f938e391dbe46baa1741ebfbb0ddd882021-11-25T16:53:11ZGalectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production10.3390/biom111116362218-273Xhttps://doaj.org/article/7f938e391dbe46baa1741ebfbb0ddd882021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1636https://doaj.org/toc/2218-273X<i>Yersinia enterocolitica</i> (Ye) inserts outer proteins (Yops) into cytoplasm to infect host cells. However, in spite of considerable progress, the mechanisms implicated in this process, including the association of Yops with host proteins, remain unclear. Here, we evaluated the functional role of Galectin-1 (Gal1), an endogenous β-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 from trypsin digestion. Given that early control of Ye infection involves activation of macrophages, we evaluated the role of Gal1 and YopP in the modulation of macrophage function. Although Gal1 and YopP did not influence production of superoxide anion and/or TNF by Ye-infected macrophages, they coordinately inhibited nitric oxide (NO) production. Notably, recombinant Gal1 (rGal1) did not rescue NO increase observed in <i>Lgals1</i><sup>−/−</sup> macrophages infected with the YopP mutant Ye ∆<i>yopP</i>. Whereas NO induced apoptosis in macrophages, no significant differences in cell death were detected between Gal1-deficient macrophages infected with Ye ∆<i>yopP</i>, and WT macrophages infected with Ye wt. Strikingly, increased NO production was found in WT macrophages treated with MAPK inhibitors and infected with Ye wt. Finally, rGal1 administration did not reverse the protective effect in Peyer Patches (PPs) of <i>Lgals1<sup>−/−</sup></i> mice infected with Ye ∆<i>yopP</i>. Our study reveals a cooperative role of YopP and endogenous Gal1 during Ye infection.Brenda Lucila JofreRicardo Javier EliçabeJuan Eduardo SilvaJuan Manuel Pérez SáezMaria Daniela PaezEduardo CallegariKarina Valeria MariñoMaría Silvia Di GenaroGabriel Adrián RabinovichRoberto Carlos DavicinoMDPI AGarticle<i>Yersinia enterocolitica</i>YopPGalectin-1nitric oxidemacrophagesMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1636, p 1636 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Yersinia enterocolitica</i> YopP Galectin-1 nitric oxide macrophages Microbiology QR1-502
spellingShingle	<i>Yersinia enterocolitica</i> YopP Galectin-1 nitric oxide macrophages Microbiology QR1-502 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 Adrián Rabinovich Roberto Carlos Davicino Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production
description	<i>Yersinia enterocolitica</i> (Ye) inserts outer proteins (Yops) into cytoplasm to infect host cells. However, in spite of considerable progress, the mechanisms implicated in this process, including the association of Yops with host proteins, remain unclear. Here, we evaluated the functional role of Galectin-1 (Gal1), an endogenous β-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 from trypsin digestion. Given that early control of Ye infection involves activation of macrophages, we evaluated the role of Gal1 and YopP in the modulation of macrophage function. Although Gal1 and YopP did not influence production of superoxide anion and/or TNF by Ye-infected macrophages, they coordinately inhibited nitric oxide (NO) production. Notably, recombinant Gal1 (rGal1) did not rescue NO increase observed in <i>Lgals1</i><sup>−/−</sup> macrophages infected with the YopP mutant Ye ∆<i>yopP</i>. Whereas NO induced apoptosis in macrophages, no significant differences in cell death were detected between Gal1-deficient macrophages infected with Ye ∆<i>yopP</i>, and WT macrophages infected with Ye wt. Strikingly, increased NO production was found in WT macrophages treated with MAPK inhibitors and infected with Ye wt. Finally, rGal1 administration did not reverse the protective effect in Peyer Patches (PPs) of <i>Lgals1<sup>−/−</sup></i> mice infected with Ye ∆<i>yopP</i>. Our study reveals a cooperative role of YopP and endogenous Gal1 during Ye infection.
format	article
author	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 Adrián Rabinovich Roberto Carlos Davicino
author_facet	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 Adrián Rabinovich Roberto Carlos Davicino
author_sort	Brenda Lucila Jofre
title	Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production
title_short	Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production
title_full	Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production
title_fullStr	Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production
title_full_unstemmed	Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production
title_sort	galectin-1 cooperates with yersinia outer protein (yop) p to thwart protective immunity by repressing nitric oxide production
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7f938e391dbe46baa1741ebfbb0ddd88
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Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production

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