Purified Staphylococcus aureus leukotoxin LukM/F′ does not trigger inflammation in the bovine mammary gland

An early recruitment of neutrophils in mammary tissue and milk is considered an important component of the defense of the mammary gland against Staphylococcus aureus. We investigated whether the leukotoxin LukM/F′, which is produced by a proportion of mastitis-causing strains of S. aureus, would be able to trigger inflammation in the udder. Infusion of purified LukM/F′ toxin in lactating mammary glands did not cause neutrophil influx in milk, showing that the toxin was not able to cause mastitis on its own. Purified LukM/F′ did not kill or stimulate mammary epithelial cells in culture. As expected, LukM bound to mammary macrophages and the complete LukM/F′ toxin killed these cells, but subcytotoxic LukM/F′ concentrations did not induce secretion of IL-8, TNF-α, IL-1β or IL-6 by macrophages. On the contrary, the production of these pro-inflammatory mediators by adhesion-stimulated macrophages was reduced. Overall, these results indicate that purified leukotoxin LukM/F′ is not likely to contribute to the initiation of the inflammatory response and could even play an anti-inflammatory role in the mammary gland by inactivating macrophages.

► Purified Staphylococcus aureus leukotoxin LukM/F′ did not induce inflammation in the mammary gland.
► LukM/F′ toxin did not kill or stimulate mammary epithelial cells in culture.
► LukM/F′ killed mammary macrophages.
► Subcytotoxic concentrations of LukM/F′ reduced macrophage secretion of inflammatory cytokines.
► The LukM/F′ leukotoxin is not pro-inflammatory in the mammary gland.