Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting

Ubiquitination, the covalent attachment of ubiquitin to proteins and other cellular substrates, is a dynamic post-translational modification that enables cells to rapidly respond to internal and external threats. Beyond its canonical role in targeting proteins for proteasomal degradation, ubiquitination orchestrates the assembly of signalling complexes that regulate innate and adaptive immune responses, modulates inflammatory pathways and directs selective autophagy to eliminate intracellular pathogens through lysosomal degradation. To persist and replicate within the host, viruses, bacteria and parasites have evolved diverse mechanisms to evade, manipulate or exploit the host's ubiquitin and autophagy machinery. Some pathogens subvert these systems to dampen immune surveillance, whereas others co-opt them to facilitate replication or dissemination. In this Review, we examine how ubiquitin and autophagy shape host-pathogen interactions, uncover common and pathogen-specific strategies of immune evasion, and discuss emerging therapeutic approaches that aim to leverage these interconnected pathways to enhance antimicrobial immunity.