O-GlcNAcylation: The crosstalk between infection immunity and autophagy in sepsis (Review)

Sepsis is a life-threatening condition triggered by dysregulated host immune responses, involving complex interactions among immune cell dysfunction, metabolic reprogramming and impaired autophagy. As a dynamic post-translational modification of serine/threonine residues, the attachment of N-acetylglucosamine (GlcNAc) via an oxygen linkage (O-GlcNAcylation) serves as a central hub in the pathogenesis of sepsis by integrating immunometabolic adaptation and autophagy regulation. This modification, dynamically controlled by O-GlcNAc transferase and O-GlcNAcase, modulates immune cell activation, inflammatory signaling and pathogen clearance. In sepsis, aberrant O-GlcNAcylation exacerbates organ damage by promoting pro-inflammatory cytokine release and suppressing protective autophagy. Studies have highlighted its dual role: Enhancing O-GlcNAcylation can bolster antiviral immunity, while targeted inhibition could mitigate bacteria-induced hyperinflammation. Furthermore, O-GlcNAcylation regulates the initiation, elongation and lysosomal fusion stages of autophagy by modifying key proteins, including beclin1, unc-51-like kinase 1 and synaptosome-associated protein 29, thereby influencing immune cell function. The present review also explores the mechanisms by which O-GlcNAcylation modulates immune responses across diverse pathogens, namely bacteria, fungi, viruses and parasites, via signaling pathways such as NF-κB and STAT, emphasizing the importance of site-specific interventions and biomarker development. In conclusion, targeting O-GlcNAcylation offers a potential novel direction for sepsis treatment. However, further exploration of its dynamic equilibrium in the precise regulation of the immune-autophagy network is necessary.

• Publication year

  2025

• Venue

  Molecular Medicine Reports

• Publication date

  2025-08-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3892/mmr.2025.13646PMID 40776755PMCID 12340768
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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