Skip to main content
Log in

Selenium Alleviates Inflammation in Staphylococcus aureus-Induced Mastitis via MerTK-Dependent Activation of the PI3K/Akt/mTOR Pathway in Mice

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Mastitis caused by Staphylococcus aureus infection not only causes serious economic losses, but also affects human health. Se plays an important role in body immunity. However, the mechanisms by which Se regulates mastitis induced by S. aureus are still principally unknown. The purpose of this study is to investigate whether Se can inhibit mastitis induced by S. aureus through regulation of MerTK. Sixty BALB/c female mice were fed low, normal, or high Se concentrations for 7 weeks and then randomly divided into six groups (Se-Low Control group (LSN), Se-Normal Control group (NSN), Se-High Control group (HSN), Se-Low S. aureus group (LSS), Se-Normal S. aureus group (NSS), Se-High S. aureus group (HSS)). The regulation of Se on MerTK was detected via histopathological staining, western blot analysis, enzyme-linked immunosorbent assay, and qRT-PCR. With increased selenium concentrations, the levels of IL-1β, IL-6, and TNF-α decreased, while the phosphorylation levels of MerTK, PI3K, AKT, and mTOR increased. Therefore, this study showed that Se could alleviate S. aureus mastitis by activating MerTK and PI3K/AKT/mTOR pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

The data of this study will be made available on reasonable request.

Code Availability

Not applicable.

References

  1. Jiang K, Ma X, Guo S, Zhang T, Zhao G, Wu H, Wang X, Deng G (2018) Anti-inflammatory effects of rosmarinic acid in lipopolysaccharide-induced mastitis in mice. Inflammation 41(2):437–448

    Article  CAS  Google Scholar 

  2. Seegers H, Fourichon C, Beaudeau F (2003) Production effects related to mastitis and mastitis economics in dairy cattle herds. Vet Res 34(5):475–491

    Article  Google Scholar 

  3. Yu Y, Zhou YF, Chen MR, Li X, Qiao GL, Sun J, Liao XP, Liu YH (2016) In vivo pharmacokinetics/pharmacodynamics of cefquinome in an experimental mouse model of Staphylococcus aureus mastitis following intramammary infusion. PLoS ONE 11(5):e0156273

  4. Scaccabarozzi L, Locatelli C, Pisoni G, Manarolla G, Casula A, Bronzo V, Moroni P (2011) Short communication: epidemiology and genotyping of Candida rugosa strains responsible for persistent intramammary infections in dairy cows. J Dairy Sci 94(9):4574–4577

    Article  CAS  Google Scholar 

  5. Ge BJ, Zhao P, Li HT, Sang R, Wang M, Zhou HY, Zhang XM (2021) Taraxacum mongolicum protects against Staphylococcus aureus-infected mastitis by exerting anti-inflammatory role via TLR2-NF-κB/MAPKs pathways in mice. J Ethnopharmacol 268:113595

  6. Peres AG, Stegen C, Li J, Xu AQ, Levast B, Surette MG, Cousineau B, Desrosiers M, Madrenas J (2015) Uncoupling of pro- and anti-inflammatory properties of Staphylococcus aureus. Infect Immun 83(4):1587–1597

    Article  CAS  Google Scholar 

  7. Wang K, Jin XL, Shen XG, Sun LP, Wu LM, Wei JQ, Marcucci MC, Hu FL, Liu JX (2016) Effects of Chinese propolis in protecting bovine mammary epithelial cells against mastitis pathogens-induced cell damage. Mediators Inflamm 2016:8028291

  8. Green M, Bradley A (2013) The changing face of mastitis control. Vet Rec 173(21):517–521

    Article  Google Scholar 

  9. Wang YS, Teng GQ, Zhou H (2021) Se deficiency induced inflammation resulting to a diminished contraction of the small intestinal smooth muscle in mice. Biol Trace Elem Res 199(4):1437–1444

    Article  CAS  Google Scholar 

  10. Li JL, Gao R, Li S, Wang JT, Tang ZX, Xu SW (2010) Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium. Biometals 23(4):695–705

    Article  CAS  Google Scholar 

  11. Duan SY, Chen SJ, Liang W, Chen MY, Chen Y, Guo MY (2021) Dietary selenium deficiency facilitated reduced stomatin and phosphatidylserine externalization, increasing erythrocyte osmotic fragility in mice. Biol Trace Elem Res 199(2):594–603.

    Article  Google Scholar 

  12. Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE, Hurst R (2011) Selenium in human health and disease. Antioxidants & Redox Signaling 14(7):1337–1383

    Article  CAS  Google Scholar 

  13. Rayman MP (2000) The importance of selenium to human health. Lancet 356(9225):233–241

    Article  CAS  Google Scholar 

  14. Mehdi Y, Hornick J-L, Istasse L, Dufrasne I (2013) Selenium in the environment, metabolism and involvement in body functions. Molecules 18(3):3292–3311

    Article  CAS  Google Scholar 

  15. Yang H, Fang J, Jia X, Han C, Chen X, Yang CS, Li N (2011) Chemopreventive effects of early-stage and late-stage supplementation of vitamin E and selenium on esophageal carcinogenesis in rats maintained on a low vitamin E/selenium diet. Carcinogenesis 32(3):381–388

    Article  CAS  Google Scholar 

  16. Liu K, Ding T, Fang L, Cui L, Li J, Meng X, Zhu G, Qian C, Wang H, Li J (2020) Organic selenium ameliorates Staphylococcus aureus-induced mastitis in rats by inhibiting the activation of NF-kappa B and MAPK signaling pathways. Front Vet Sci 7:443

    Article  Google Scholar 

  17. Wang J, Lian S, He X, Yu D, Liang J, Sun D, Wu R (2018) Selenium deficiency induces splenic growth retardation by deactivating the IGF-1R/PI3K/Akt/mTOR pathway. Metallomics 10(11):1570–1575

    Article  CAS  Google Scholar 

  18. O’Neill LAJ (2007) TAMpering with toll-like receptor signaling. Cell 131(6):1039–1041

    Article  CAS  Google Scholar 

  19. Triantafyllou E, Pop O, Possamai L, Wilhelm A, Liaskou E, Petts G, Singanayagam A, Bernsmeier C, Khamri W, Patel V, Stamataki Z, Curbishley S, Ma Y, Woollard K, Quaglia A, Wendon J, Thursz M, Adams D, Weston C, Antoniades C (2018) MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure. Gut 67(2):333–347

    Article  CAS  Google Scholar 

  20. Lemke G, Rothlin CV (2008) Immunobiology of the TAM receptors. Nat Rev Immunol 8(5):327–336

    Article  CAS  Google Scholar 

  21. Li Y, Wittchen ES, Monaghan-Benson E, Hahn C, Earp HS, Doerschuk CM, Burridge K (2019) The role of endothelial MERTK during the inflammatory response in lungs. PLoS One 14(12):e0225051

    Article  CAS  Google Scholar 

  22. Yang J, Li SY, Wang LY, Du F, Zhou XL, Song QQ, Zhao JL, Fang R (2018) Ginsenoside Rg3 attenuates lipopolysaccharide-induced acute lung injury via MerTK-dependent activation of the PI3K/AKT/mTOR pathway. Front Pharmacol 9:850

    Article  Google Scholar 

  23. van der Meer JHM, van der Poll T, van’t Veer C (2014) TAM receptors, Gas6, and protein S roles in inflammation and hemostasis. Blood 123(16):2460–2469

    Article  CAS  Google Scholar 

  24. Bi CL, Zhang SJ, Shen YZ, Pauline M, Li H, Tang H (2021) Selenium plays an anti-inflammatory role by regulation NLRP3 inflammasome in Staphylococcus aureus-infected mouse mammary gland. Biol Trace Elem Res 199(2):604–610

    Article  CAS  Google Scholar 

  25. Schmidt T, Kock MM, Ehlers MM (2017) Molecular characterization of Staphylococcus aureus isolated from bovine mastitis and close human contacts in South African dairy herds: genetic diversity and inter-species host transmission. Front Microbiol 8:511

    Article  Google Scholar 

  26. Ren ZH, Bai LP, Shen LH, Luo ZZ, Zhou ZH, Zuo ZC, Ma XP, Deng JL, Wang Y, Xu SY, Luo YH, Cao SZ, Yu SM (2020) Comparative iTRAQ proteomics reveals multiple effects of selenium yeast on dairy cows in parturition. Biol Trace Elem Res 197(2):464–474

    Article  CAS  Google Scholar 

  27. Weichhart T, Hengstschlager M, Linke M (2015) Regulation of innate immune cell function by mTOR. Nat Rev Immunol 15(10):599–614

    Article  CAS  Google Scholar 

  28. Zhang RL, Guo R, Liu Q, Li GX, Sun B, Huang XD (2020) Selenium deficiency via the TLR4/TRIF/NF-κB signaling pathway leading to inflammatory injury in chicken spleen. Biol Trace Elem Res 199(2):693–702

    Article  Google Scholar 

  29. Ma J, Zhu S, Guo Y, Hao M, Chen Y, Wang Y, Yang M, Chen J, Guo M (2019) Selenium attenuates Staphylococcus aureus mastitis in mice by inhibiting the activation of the NALP3 inflammasome and NF-κB/MAPK pathway. Biol Trace Elem Res 191(1):159–166

    Article  CAS  Google Scholar 

  30. Jing HY, Wang SC, Wang Y, Shen NW, Gao XJ (2020) Environmental contaminant ammonia triggers epithelial-to-mesenchymal transition-mediated jejunal fibrosis with the disassembly of epithelial cell-cell contacts in chicken. Sci Total Environ 726:138686

  31. Klebanoff SJ (2005) Myeloperoxidase: friend and foe. J Leukoc Biol 77(5):598–625

    Article  CAS  Google Scholar 

  32. Sun W, Zhu J, Li S, Tang C, Zhao Q, Zhang J (2020) Selenium supplementation protects against oxidative stress-induced cardiomyocyte cell cycle arrest through activation of PI3K/AKT. Metallomics 12(12):1965–1978

    Article  CAS  Google Scholar 

  33. Jing H, Zhang Q, Gao X (2021) Excessive lithium of water induced a toxic effect on kidney via oxidative damage and inflammation in carp. Aquaculture 535:736282

    Article  CAS  Google Scholar 

  34. Li X, Zhao X, Yao Y, Guo M, Li S (2021) New insights into crosstalk between apoptosis and necroptosis co-induced by chlorothalonil and imidacloprid in Ctenopharyngodon idellus kidney cells. Sci Total Environ 780:146591

    Article  CAS  Google Scholar 

  35. Wang L, Shi X, Zheng S, Xu S (2020) Selenium deficiency exacerbates LPS-induced necroptosis by regulating miR-16-5p targeting PI3K in chicken tracheal tissue. Metallomics 12(4):562–571

    Article  CAS  Google Scholar 

  36. Geng N, Liu K, Lu J, Xu Y, Wang X, Wang R, Liu J, Liu Y, Han B (2020) Autophagy of bovine mammary epithelial cell induced by intracellular Staphylococcus aureus. J Microbiol 58(4):320–329

    Article  CAS  Google Scholar 

  37. Song N, Wang W, Wang Y, Guan YL, Xu SW, Guo MY (2021) Hydrogen sulfide of air induces macrophage extracellular traps to aggravate inflammatory injury via the regulation of miR-15b-5p on MAPK and insulin signals in trachea of chickens. Sci Total Environ 771:145407

  38. Chen F, Castranova V, Shi X, Demers LM (1999) New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem 45(1):7–17

    Article  CAS  Google Scholar 

  39. Eken C, Martin PJ, Sadallah S, Treves S, Schaller M, Schifferli JA (2010) Ectosomes released by polymorphonuclear neutrophils induce a MerTK-dependent anti-inflammatory pathway in macrophages. J Biol Chem 285(51):39914–39921

    Article  CAS  Google Scholar 

  40. Zhang B, Fang L, Wu HM, Ding PS, Xu K, Liu RY (2016) Mer receptor tyrosine kinase negatively regulates lipoteichoic acid-induced inflammatory response via PI3K/Akt and SOCS3. Mol Immunol 76:98–107

    Article  CAS  Google Scholar 

Download references

Funding

This study was funded by the National Key Research and Development Plan (No. 2016YFD0500906) and the special fund for the China Agriculture Research System (Beef/Yak cattle) (No. CARS-37), National Natural Science Foundation of China (No. 31101874, 31972758), Key R & D program of Hubei province of China (No. 2020BBA055), and the Research Fund for National Distinguished Scholars in Agriculture Research and Technical Innovative Team, the Provincial Innovation and Entrepreneurship Training Program for Undergraduate (No. S202010504023).

Author information

Authors and Affiliations

Authors

Contributions

S. C., and C. Z. conceived and designed the experiments. S. C., C. Z., D. Y., C. L., and H. X. carried out the experiments. S. C., and C. Z. processed the data. S. C., C. Z., and C. H. wrote the paper. The final manuscript was read and approved by all authors.

Corresponding author

Correspondence to Chang-min Hu.

Ethics declarations

Ethics Approval and Consent to Participate

All the animal experiments involved in this paper have been approved by the Animal Research Ethics Committee of Huazhong Agricultural University (HZAUMO-2021–0016).

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Sj., Zhang, Cy., Yu, D. et al. Selenium Alleviates Inflammation in Staphylococcus aureus-Induced Mastitis via MerTK-Dependent Activation of the PI3K/Akt/mTOR Pathway in Mice. Biol Trace Elem Res 200, 1750–1762 (2022). https://doi.org/10.1007/s12011-021-02794-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-021-02794-z

Keywords

Navigation