The role of TRIM proteins in the pathogenesis of mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen responsible for tuberculosis (TB), a disease that remains the leading infectious cause of death worldwide. Several host cell proteins have been reported to play a significant role in regulating Mtb infection and replication. Among these, TRIM proteins are a large family of E3 ubiquitin ligases that have been described as being involved in host defence against Mtb, by controlling two important cellular processes: autophagy and the inflammatory response. Autophagy is a highly conserved cellular process deputed to the degradation of damaged or unnecessary components, such as organelles and protein aggregates. Autophagy is induced by a variety of stress stimuli, including nutrient deprivation, hypoxia, infection, oxidative stress and DNA damage, to maintain cellular homeostasis and survival. Autophagy plays a crucial role in host defense against infections by selectively targeting and delivering intracellular pathogens, like bacteria, viruses, and parasites to the lysosomes for degradation. Inflammation is a biological coordinated cellular process involving the secretion of cytokines and chemokines by innate immune cells, that can be triggered by various factors, including damaged cells, toxins and pathogens. Pathogen-Associated Molecular Patterns (PAMPs), found on microbes, are recognized by pattern recognition receptors (PRRs) on immune cells, which trigger signaling pathways leading to pro-inflammatory responses and the elimination of the pathogen. Danger-Associated Molecular Patterns (DAMPs) are host-derived molecules released from damaged cells that activate the same PRRs to initiate or perpetuate inflammation. In this review, we discuss the emerging role played by TRIM proteins in regulating autophagy and pro-inflammatory response during Mtb infection, pointing out the crucial role of TRIM in the complex crosstalk between these processes.Not applicable.