The crosstalk between SUMOylation and immune system in host-pathogen interactions

Pathogens can not only cause infectious diseases, immune system diseases, and chronic diseases, but also serve as potential triggers or initiators for certain tumors. They directly or indirectly damage human health and are one of the leading causes of global deaths. Small ubiquitin-like modifier (SUMO) modification, a type of protein post-translational modification (PTM) that occurs when SUMO groups bond covalently to particular lysine residues on substrate proteins, plays a crucial role in both innate and adaptive immunologic responses, as well as pathogen-host immune system crosstalk. SUMOylation participates in the host's defense against pathogens by regulating immune responses, while numerically vast and taxonomically diverse pathogens have evolved to exploit the cellular SUMO modification system to break through innate defenses. Here, we describe the characteristics and multiple functions of SUMOylation as a pivotal PTM mechanism, the tactics employed by various pathogens to counteract the immune system through targeting host SUMOylation, and the character of the SUMOylation system in the fight between pathogens and the host immune system. We have also included a summary of the potential anti-pathogen SUMO enzyme inhibitors. This review serves as a reference for basic research and clinical practice in the diagnosis, prognosis, and treatment of pathogenic microorganism-caused disorders.