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

Kai Zhang; Yan Jia; Yinghong Qian; Xueying Jiang; Shuangyi Zhang; Bo Liu; Jinshan Cao; Yongli Song; Wei Mao

doi:10.3389/fmicb.2023.1163261

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

Front Microbiol. 2023 Apr 24:14:1163261. doi: 10.3389/fmicb.2023.1163261. eCollection 2023.

Authors

Kai Zhang^#^{1

2}, Yan Jia^#^{1

2}, Yinghong Qian³, Xueying Jiang^{1

2}, Shuangyi Zhang^{1

2}, Bo Liu^{1

2}, Jinshan Cao^{1

2}, Yongli Song⁴, Wei Mao^{1

2}

Affiliations

¹ College of Veterinary Medicine, Inner Mongolia Agricultural University, Huhhot, China.
² Key Laboratory of Animal Clinical Treatment Technology, Ministry of Agriculture, Huhhot, China.
³ Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Huhhot, China.
⁴ Stem Cell and Microbiology, Inner Mongolia University, Huhhot, China.

^# Contributed equally.

Abstract

Introduction: In 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.

Methods: In 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.

Results: The 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.

Discussion: Taken 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.

Keywords: NLR pyrin domain-containing 3; Prostaglandin E2; Staphylococcus aureus; neutrophils; toll-like receptor 2; toll-like receptor 4.

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (31860720), the Innovative Research Team in Universities of Inner Mongolia Autonomous Region (NJYT22041), and the Natural Science Foundation of Inner Mongolia Autonomous Region (2022MS03048).