increases Prostaglandin E secretion in cow neutrophils by activating TLR2, TLR4, and NLRP3 inflammasome signaling pathways.

Introduction: In clinical settings, dairy cows are often attacked by pathogenic bacteria after delivery, especially (). Neutrophils have long been regarded as essential for host defense against . Prostaglandin E (PGE) can additionally be used as an inflammatory mediator in pathological conditions to promote the repair of inflammatory injuries. However, whether can promote the accumulation of PGE after the infection of neutrophils in cows and its mechanism remain unclear. Lipoprotein is an important immune bioactive ingredient of .

Methods: In this study, the changes in neutrophils were monitored in dairy cows infected with wild-type (SA113) and an lipoprotein-deficient strain (Δ); meanwhile, we established whether pattern recognition receptors mediate this process and whether lipoproteins are necessary for causing the release of PGE from cow neutrophils.

Results: The results showed that Δ was less effective than SA113 in inducing the production of IL-1β, IL-6, IL-8, IL-10, and PGE within neutrophils; furthermore, TLR2, TLR4, and NLRP3 receptors were found to mediate the inducible effect of lipoprotein on the above inflammation mediators and cytokines, which depended on MAPK and Caspase-1 signaling pathways. In addition, TLR2, TLR4, and NLRP3 inhibitors significantly inhibited PGE and cytokine secretion, and PGE was involved in the interaction of and neutrophils in dairy cows, which could be regulated by TLR2, TLR4, and NLRP3 receptors. We also found that was more likely to be killed by neutrophils when it lacked lipoprotein and TLR2, TLR4, and NLRP3 were involved, but PGE seemed to have no effect.

Discussion: Taken together, these results suggest that lipoprotein is a crucial component of in inducing cytokine secretion by neutrophils as well as killing within neutrophils, which could be accomplished by the accumulation of PGE by activating MAPK and the Caspase-1 signaling pathways through TLR2, TLR4, and NLRP3 receptors. These results will contribute to a better understanding of the interaction between and host immune cells in dairy cows.