Exploring the potential immunomodulatory effects of gallic acid on milk phagocytes in bovine mastitis caused by Staphylococcus aureus

Bovine mastitis caused by Staphylococcus aureus may exacerbate by resulting in significant economic losses and impacting milk quality. To date, the use of gallic acid, a phenolic compound naturally occurring in various plants, holds promise due to its potent anti-oxidant and anti-inflammatory effects in many pieces of literature, thus, making it a subject of interest in bovine innate immunity research. Here we used gallic acid to assess its potential immunomodulation on milk phagocytes in vitro challenges with mastitis-causing bacteria. Our findings indicated that cells exposed to gallic acid showed no harm to cell viability but might maintain the longevity of cells during the bacterial infection. Gallic acid-treated cells displayed reduced cell migration, phagocytosis, and bacterial killing ability, while showing an increase in ROS production, all of which are undoubtedly linked to the intracellular killing abilities of the cells. Nonetheless, the extracellular structure called neutrophil extracellular traps (NETs) was significantly released after receiving gallic acid, representing extracellular killing. We also reported that gallic acid neutralizes inflammation by regulating specific pro-inflammatory genes (IL1B, IL6, TNF) and ROS-generating genes (CYBA, LAMP1, RAC1), subsequently preventing tissue damage. Regarding apoptosis-related genes and proteins, the increased production of caspase-3 and Bcl-2 family proteins could potentially promote the longevity of cells, implicated in the mechanism of combating bacterial invasion during udder inflammation and infection. The novel role of gallic acid on milk phagocytes highlights its potential immunomodulatory properties and contributes to our understanding of its effects on bacterial-host interactions, and provides valuable molecular insights.