Staphylococcus aureus increases Prostaglandin E2 secretion in cow neutrophils by activating TLR2, TLR4, and NLRP3 inflammasome signaling pathways

Abstract

IntroductionIn clinical settings, dairy cows are often attacked by pathogenic bacteria after delivery, especially Staphylococcus aureus (S. aureus). Neutrophils have long been regarded as essential for host defense against S. aureus. Prostaglandin E2 (PGE2) can additionally be used as an inflammatory mediator in pathological conditions to promote the repair of inflammatory injuries. However, whether S. aureus can promote the accumulation of PGE2 after the infection of neutrophils in cows and its mechanism remain unclear. Lipoprotein is an important immune bioactive ingredient of S. aureus.MethodsIn this study, the changes in neutrophils were monitored in dairy cows infected with wild-type S. aureus (SA113) and an S. aureus lipoprotein-deficient strain (Δlgt); meanwhile, we established whether pattern recognition receptors mediate this process and whether S. aureus lipoproteins are necessary for causing the release of PGE2 from cow neutrophils.ResultsThe results showed that Δlgt was less effective than SA113 in inducing the production of IL-1β, IL-6, IL-8, IL-10, and PGE2 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 PGE2 and cytokine secretion, and PGE2 was involved in the interaction of S. aureus and neutrophils in dairy cows, which could be regulated by TLR2, TLR4, and NLRP3 receptors. We also found that S. aureus was more likely to be killed by neutrophils when it lacked lipoprotein and TLR2, TLR4, and NLRP3 were involved, but PGE2 seemed to have no effect.DiscussionTaken together, these results suggest that lipoprotein is a crucial component of S. aureus in inducing cytokine secretion by neutrophils as well as killing within neutrophils, which could be accomplished by the accumulation of PGE2 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 S. aureus and host immune cells in dairy cows.

Dynamic m6A profiles reveal the role of YTHDC2‐TLR2 signaling axis in Talaromyces marneffei infection

“…Even Katalin et al reported that m 6 A modifications suppress the ability of RNA to stimulate TLR3, TLR7, and TLR8, 38 they did not uncover the m 6 A-regulated expression level of TLR2, and our findings fill this knowledge gap. In fact, TLR2 is regulated by various mechanisms like infection and gut microbes, [39][40][41] and we have just discovered that m 6 A might be a regulatory mechanism during the TM infection process. Previous studies have shown that YTHDC2 primarily regulates RNA degradation through m 6 A modification.…”

Effect of 2% meloxicam injection in Holstein dairy cows on acute clinical mastitis without systemic symptoms

“…S. aureus has been reported to increase secretion of cytokines in bovine neutrophils. In dairy cow infected with wild-type S. aureus (SA113) and a lipoprotein-deficient strain of S. aureus (Δlgt), Δlgt was less effective than SA113 in inducing the production of IL-1β, IL-6, IL-8, IL-10, and PGE 2 within neutrophils [ 14 ]. In our study, a significant negative correlation ( P <0.05) was found between whey PGE 2 concentrations and LS on day 1 in the T group but not in the C group.…”

Divergent Immune Responses to Minor Bovine Mastitis-Causing Pathogens

“…Investigating apoptosis at different time points could provide additional insights [ 24 ]. Although exposure to TLR ligands did not trigger apoptosis in bovine PMNs [ 25 ], their involvement in inflammasome activation and subsequent silent cell death through pyroptosis cannot be ruled out [ 19 ]. Investigating other cell death pathways, like necrosis, NETosis, and pyroptosis, could be informative as bovine neutrophils might employ alternative mechanisms against minor pathogens [ 15 , 20 , 26 ].…”

“…Unraveling how bovine neutrophils recognize “minor players” like NASM and LAB, especially S. chromogenes , holds the key to understanding udder immunity dynamics. Upon pathogen recognition, bovine neutrophils wage war with classical tactics (phagocytosis, ROS, RNI, AMPs, granule enzymes) [ 17 ], and subtle strategies (NETs, inflammatory mediators) for comprehensive udder defense unfold [ 15 , 18 , 19 , 20 , 21 ]. Adding another layer to their defense, neutrophils undergo programmed death (apoptosis) to limit NASM and LAB infections and resolve inflammation, revealing the intricate interplay between host and pathogen.…”