Emerging role of lipid droplets in obscure puffer immune response against Vibrio harveyi.

As dynamic and functionally active organelles, lipid droplets (LDs) mainly function in lipid anabolism, while recent studies showed that mammalian LDs also actively participated in innate immunity; however, the specific roles and regulation mechanism remain relatively unexplored, and the existing studies were mainly limited to mammals. In the present study, we first found that Vibrio harveyi, a serious pathogen in marine environment, could induce LDs accumulation in the liver of obscure puffer Takifugu obscurus on the histology, morphology and molecular levels, and the induction mainly conducted by promoting the synthesis of neutral lipids. Moreover, the antibacterial activity of LD proteins was significantly enhanced upon V. harveyi stimulation, and showed broad-spectrum characteristic. While the inhibition of LDs formation downregulated the expression of immune-related genes and immune signaling elements, highlighting the potential critical roles of LDs during the bacterial infection. The isolated LDs from obscure puffer liver were examined via proteomic analyses, and the data supported the conservative property of LDs from bacteria to humans, and revealed that numerous innate immune system-related components were enriched on the surface of LDs. These results will deepen the understanding of LDs biology and host immune defense mechanism, shedding light on the new strategies for the development of anti-infective therapies.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-025-00286-w.