Post-translational modifications: Bridging viral infections and inflammatory bowel disease

Abstract

Macrophages are key innate immune cells that defend against pathogens, maintain tissue homeostasis, and regulate inflammation. A complex network of post-translational modifications (PTMs) controls the flexibility and adaptability of macrophage functions. These modifications change the structure, function, location, and interactions of proteins through covalent mechanisms such as phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation. This enables macrophages to respond quickly and accurately to changes in their microenvironment. Dysregulated macrophage function is pivotal to the pathophysiology of inflammatory bowel disease (IBD) and the resultant outcomes following viral infections. Recent evidence suggests that macrophage PTMs provide a mechanistic link between IBD and viral infection. Viral infections may accelerate disease onset or exacerbate IBD activity. Viruses exploit the PTM machinery of host cells for their replication and immune evasion. This review discusses how PTM changes in macrophages caused by viral infections can lead to a long-lasting, pro-inflammatory state that could tip the balance of intestinal immunity toward chronic IBD. We elucidate the functions of traditional PTMs such as phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation, in conjunction with emerging modifications such as lactylation and citrullination (deimination). We emphasize their distinct roles in both antiviral responses and IBD pathogenesis, while also exploring therapeutic strategies targeting PTM pathways.