The Yin-Yang of lipid droplets in pathogenic bacterial infection: from immunological guardian to pathogenic exploitation

Lipid droplets (LDs) are dynamic and multifunctional organelles composed of a hydrophobic core of neutral lipids, a monolayer phospholipid shell, and various associated proteins. They play a critical role in diverse processes such as lipid storage, energy metabolism, membrane trafficking, and cellular signaling, thus linking them to a variety of diseases, including metabolic disorders, cancer, and infectious diseases. In host-pathogen interactions, LDs exhibit a “Yin-Yang” dual role: on the one hand, as a core component of the host interferon response, LDs not only serve as key hubs for activating interferon-signaling pathways but also help establish an effective innate immune defense by modulating the intensity of the immune response in the early stages of pathogen infection. On the other hand, various pathogens hijack LDs through mechanisms such as lipolysis regulation and membrane fusion, utilizing them as nutrient sources and membrane components to create an intracellular niche favorable for their own replication. While existing literature has reviewed the biogenesis and physiological functions of LDs within cells, this review focuses on the roles and molecular mechanisms of LDs in innate immunity and bacterial infections, thereby providing new perspectives for developing LD-based anti-infective therapeutics.