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YopP from Yersinia enterocolitica targets surface N-Glycans to modulate nitric oxide production in macrophage

Juan Agustín Garay¹, Juan Eduardo Silva¹, Brenda Jofre²

¹Laboratory of Immunopathology and Flow Cytometry, IMIBIO-SL (CONICET-UNSL), San Luis, Argentina; Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.

Microbial Pathogenesis

|July 16, 2026

Abstract:

Yersinia enterocolitica outer protein P (YopP), a key virulence factor, is known to modulate the early host immune response. This study investigated the interaction between YopP and N-glycans on peritoneal macrophages, as well as the subsequent effects on nitric oxide (NO) production. Our findings show that YopP is released into the supernatants of Yersinia enterocolitica-infected macrophages cultures and that Yops bind to the cell surface. We further demonstrate that both YopP and N-glycans contribute to Yops release, and that Yops binding to the macrophage surface is glycan-dependent. Notably, the removal of N-glycans from surface macrophages significantly reduced NO production in vitro. Under these conditions, YopP exhibited a dual function: it suppressed NO production in non-deglycosylated macrophages but enhanced it in N-glycan-deficient macrophages, underscoring the critical role of N-glycans in the regulatory activity of YopP. Unexpectedly, the inhibitory effect of YopP on NO was found to be sialic-acid dependent and was reversed by lactose addition. In vivo experiments further confirmed the importance of N-glycans in YopP-mediated regulation of NO in infected mice. Furthermore, our findings indicate that necroptosis plays a role in YopP-induced cell death, which may, facilitate the extracellular release of Yops. In summary, this study demonstrates that YopP modulates the early immune response through a previously unrecognized mechanism involving its interaction with macrophages N-glycans. These findings reveal a complex interplay between Y. enterocolitica and its host, offering new insights into the mechanisms underlying infection.

Insights

Yersinia enterocolitica outer protein P (YopP) interacts with macrophage N-glycans, altering nitric oxide (NO) production. This glycan-dependent interaction reveals a new mechanism in Y. enterocolitica infection.

Area of Science:

Immunology
Microbiology
Glycobiology

Background:

Yersinia enterocolitica outer protein P (YopP) is a critical virulence factor modulating host immune responses.
The role of host cell surface glycans in bacterial effector protein interaction and immune modulation is increasingly recognized.

Purpose of the Study:

To investigate the interaction between YopP and N-glycans on peritoneal macrophages.
To determine the impact of this interaction on nitric oxide (NO) production.
To elucidate the mechanism of YopP-mediated immune modulation in Yersinia enterocolitica infection.

Main Methods:

Investigated YopP interaction with peritoneal macrophages.
Assessed the role of N-glycans in YopP binding and release.
Measured nitric oxide (NO) production in vitro and in vivo.
Analyzed the effect of N-glycan removal and sialic acid on YopP activity.
Examined the role of necroptosis in YopP-mediated cell death.

Main Results:

YopP is released extracellularly and binds to macrophage surfaces in a glycan-dependent manner.
N-glycans are crucial for YopP's regulatory activity, exhibiting dual effects on NO production based on their presence.
YopP's inhibitory effect on NO is sialic acid-dependent and reversible by lactose.
In vivo studies confirmed the importance of N-glycans in YopP-mediated NO regulation.
Necroptosis contributes to YopP-induced cell death and Yops release.

Conclusions:

YopP modulates the early immune response via a novel mechanism involving interaction with macrophage N-glycans.
N-glycans play a critical role in regulating YopP's function and the host's immune response to Yersinia enterocolitica.
This study provides new insights into the complex interplay between Y. enterocolitica and its host immune system.

Read full analysis

Keywords:

Cell death Enterobacteria Glycoproteins Innate immunity iNOS

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