Skip to main content
Log in

Selenium Plays an Anti-Inflammatory Role by Regulation NLRP3 Inflammasome in Staphylococcus aureus-Infected Mouse Mammary Gland

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

Abstract

Selenium is an essential micronutrient that plays an important role in immunity. However, the mechanism that Selenium modulates mastitis is not fully clear. In this experiment, we investigated whether selenium can inhibit the activation of the NLRP3 inflammasome in a mouse model of Staphylococcus aureus-induced mastitis. Eighty BALB/c female mice were fed with experimental Selenium deficiency basal diet for 2 weeks to achieve the purpose of selenium consumption until pregnancy. Pregnant mice were randomly divided into four groups (control group; selenium supplement group; Staphylococcus aureus infection group and Staphylococcus aureus infection after selenium supplement group). Twenty-four hours after challenging, all mice were euthanized and mammary tissue samples were aseptically collected. Through pathological staining, western blot analysis, real-time fluorescence quantitative polymerase chain reaction analysis, and enzyme-linked immunosorbent assay, the regulation effect of Selenium on NLRP3 inflammasome was detected. The result showed that compared with the control group, selenium significantly inhibited the expression of NLRP3, ASC, Caspase-1, Caspase-1 p20, and Pro-IL-1β (p < 0.01). Meanwhile the mRNA expression and release of IL-1β was suppressed in the treatment group compared with Staphylococcus aureus infection group (p < 0.01). Therefore, these results suggest that dietary selenium can attenuate Staphylococcus aureus mastitis by inhibition of the NLRP3 inflammasome.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

All data used during the study appear in the submitted article.

References

  1. Hoque MN, Das ZC, Rahman ANMA et al (2018) Molecular characterization of Staphylococcus aureus strains in bovine mastitis milk Bangladesh. Int J Sci Med 6(1):53–60

    CAS  Google Scholar 

  2. Rahmeto A, Ha H, Mesele A et al (2016) Bovine mastitis: prevalence, risk factors and isolation of Staphylococcus aureus in dairy herds at Hawassa milk shed. South Ethiopia BMC Vet Res 12:270

    Article  Google Scholar 

  3. Tracy S, Marleen MK, Marthie ME (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

    Google Scholar 

  4. Zhang LM, Gao J, Herman WB et al (2018) Virulence gene profiles: alpha-hemolysin and clonal diversity in Staphylococcus aureus isolates from bovine clinical mastitis in China. BMC Vet Res 14:63

    Article  Google Scholar 

  5. Dominique B, Daniel S, Andrea TF et al (2014) Staphylococcus aureus from 152 cases of bovine, ovine and caprine mastitis investigated by multiple-locus variable number of tandem repeat analysis (MLVA). Vet Res 45(1):97

    Article  Google Scholar 

  6. Alva-Murillo N, Ochoa-Zarzosa A, López-Meza J (2017) Sodium octanoate modulates the innate immune response of bovine mammary epithelial cells through the TLR2/P38/JNK/ERK1/2 pathway: implications during Staphylococcus aureus internalization. Front Cell Infect Microbiol 7:78

    Article  Google Scholar 

  7. Swinkels JM, Lam TJGM, Green MJ, Bradley AJ (2013) Effect of extended cefquinome treatment on clinical persistence or recurrence of environmental clinical mastitis. Vet J 197(3):682–687

    Article  CAS  Google Scholar 

  8. Youcef M, Isabelle D (2016) Selenium in cattle: a review. Molecules. 21(3):545

    Google Scholar 

  9. Qazi IH, Angel C, Yang HX et al (2018) Selenium, sialoproteins, and female reproduction: a review. 23: 3053

  10. Bozena H, Marta K, Sylvie S et al (2017) A summary of new findings on the biological effects of selenium in selected animal species-a critical review. Int J Mol Sci 18(10):2209

    Article  Google Scholar 

  11. Zhang W, Zhang R, Wang T, Jiang H, Guo M, Zhou E, Sun Y, Yang Z, Xu S, Cao Y, Zhang N (2014) Selenium inhibits LPS-induced pro-inflammatory gene expression by modulating MAPK and NF-κB signaling pathways in mouse mammary epithelial cells in primary culture. Inflammation 37:478–485

    Article  CAS  Google Scholar 

  12. Sordillo LM (2016) Nutritional strategies to optimize dairy cattle immunity. J Dairy Sci 99(6):4967–4982

    Article  CAS  Google Scholar 

  13. Smith AD, Cheung L, Beshah E, Shea-Donohue T, Urban JF Jr (2013) Selenium status alters the immune response and expulsion of adult Heligmosomoides bakeri worms in mice. Infect Immun 81:2546–2553

    Article  CAS  Google Scholar 

  14. Marek K, Stanislaw B (2016) Current knowledge on the importance of selenium in food for living organism; a review. Melecules. 21(5):609

    Article  Google Scholar 

  15. Hoque MN, Das ZC, Rahman ANMA, Hoque MM (2016) Effect of administration of vitamin E, selenium and antimicrobial therapy on incidence of mastitis, productive and reproductive performances in dairy cows. Int J Vet Med 4(2):63–70

    Article  CAS  Google Scholar 

  16. Angelica RJ, Ninoska C, Juan A et al (2016) Antibacterial effect of copper on microorganisms isolated from bovine mastitis. Front Microbiol 7:626

    Google Scholar 

  17. Lorraine MS (2013) Selenium-dependent regulation of oxidative stress and immunity in periparturient dairy cattle. Vet Med Int 2013:154045

    Google Scholar 

  18. Gao XJ, Zhang ZC, Li Y, Shen P, Hu X, Cao Y, Zhang N (2016) Selenium deficiency facilitates inflammation following S. aureus infection by regulating TLR2-related pathways in the mouse mammary gland. Biol Trace Elem Res 172:449–457

    Article  CAS  Google Scholar 

  19. Wang H, Bi CL, Wang YJ et al (2018) Selenium ameliorates Staphylococcus aureus-induced inflammation in bovine mammary epithelial cells by inhibiting activation of TLR2, NF-κB and MAPK signaling pathways. BMC Vet Res 14:197

    Article  Google Scholar 

  20. Jason HM, David BAJ, Ashley LD et al (2015) Staphylococcus aureus Leukocidin A/B(LukAB) kills human monocytes via host NLRP3 and ASC when extracellular, but not intracellular. PLoS Pathog 11(6):e1004970

    Article  Google Scholar 

  21. Zhao XB, Pu DB, Zhao ZZ, Zhu H, Li H, Shen Y, Zhang X, Zhang R, Shen J, Xiao W, Chen W (2017) Teuvincenone F suppresses LPS-induced inflammation and NLRP3 Inflammasome activation by attenuating NEMO ubiquitination. Front Pharmacol 8:565

    Article  CAS  Google Scholar 

  22. Yang ZF, Xian HF, Hu JJ, Tian S, Qin Y, Wang RF, Cui J (2015) USP18 negatively regulates NF-kappa B signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms. Sci Rep 5:12738

    Article  CAS  Google Scholar 

  23. Kebaier C, Chamberland RR, Allen IC, Gao X, Broglie PM, Hall JD, Jania C, Doerschuk CM, Tilley SL, Duncan JA (2012) Staphylococcus aureus alpha-hemolysin mediates virulence in a murine model of severe pneumonia through activation of the NLRP3 inflammasome. J Infect Dis 205:807–817

    Article  CAS  Google Scholar 

  24. Lee DJ, Du F, Chen SW et al (2015) Regulation and function of the caspase-1 in an inflammatory microenvironment. J Invest Dermatol 135(8):2012–2020

    Article  CAS  Google Scholar 

  25. Li YF, Gayani N, Sun Y et al (2017) Analyses of caspase-1-regulated transcriptomes in various tissues lead to identification of novel IL-1β-, IL-8- and sirtuin-1-independent pathway. J Hematol Oncol 10:40

    Article  Google Scholar 

  26. Bi CL, Wang H, Wang YJ, Sun J, Dong JS, Meng X, Li JJ (2016) Selenium inhibits Staphylococcus aureus induced inflammation by suppressing the activation of the NF-κB and MAPK signaling pathways in raw264.7 macrophages. Eur J Pharmacol 780:159–165

    Article  CAS  Google Scholar 

  27. Natayme RT, Koen B, Evelyne M et al (2018) Staphylococcus aureus extracellular vesicles elicit an immunostimulatory response in vivo on the murine mammary gland. Front Cell Infect Microbiol 8:277

    Article  Google Scholar 

  28. Jully GT, Vincent W, Charlene BW et al (2017) Mammary gland pathology subsequent to acute infection with strong versus weak biofilm forming staphylococcus aureus bovine mastitis isolates: a pilot study using non-invasive mouse mastitis model. PLoS One 12(1):e0170668

    Article  Google Scholar 

  29. Wang H, Zhou YQ, Zhu QC et al (2019) Staphylococcus aureus induceds autophagy in bovine mammary epithelial and formation of autophagosomes facilitates intracellular replicellular replication of Staph. aureus. J. Dairy Sci 102:16414

    Google Scholar 

  30. Cai J, Li J, Zhou YQ et al (2020) Staphylococcus aureus facilitates its survival in bovine macrophages by blocking autophagic flux. J Cell Mol Med 00:1–9

    Google Scholar 

  31. Wang H, Yu GT, Yu H, Gu M, Zhang J, Meng X, Liu Z, Qiu C, Li J (2015) Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model. Acta Vet Scand 57:25

    Article  Google Scholar 

  32. Nathan K, Devon J, Duan YH et al (2019) The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci 20(13):3328

    Article  Google Scholar 

  33. Marine G, Bénédicte FP (2018) Spotlight on the NLRP3 inflammasome pathway. J Inflamm Res 11:359–374

    Article  Google Scholar 

  34. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E (2010) NLRP3 inflammasome are required for atherogenesis and activated by cholesterol crystals. Nature. 464:1357–1361

    Article  CAS  Google Scholar 

  35. Ma JK, Zhu S, Guo YF, 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 NLRP3 inflammasome and NF-κB/MAPK pathway. Biol Trace Elem Res 191:159–166

    Article  CAS  Google Scholar 

  36. Zhang HF, Zhao MG, Liang GB, Song ZQ, Li ZQ (2013) Expression of pro-inflammatory cytokines and the risk of intracranial aneurysm. Inflammation. 36:1195–1200

    Article  CAS  Google Scholar 

  37. Chaudhry H, Zhou J, Zhong Y et al (2013) Role of cytokines as a double-edged sword in sepsis. Vivo. 27:669

    CAS  Google Scholar 

  38. Song C, He L, Zhang J, Ma H, Yuan X, Hu G, Tao L, Zhang J, Meng J (2016) Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the activation of NALP3 inflammasome and IL-1β/IL-1R1/MyD88/NF-κB pathway. J Cell Mol Med 20:2064–2077

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (NO. 31802254), the Science and Technology Project of Shandong Province Higher Education Institutions (J18KB074), and the Key Research and Development Project of Hebei (19226625D).

Author information

Authors and Affiliations

Authors

Contributions

Chong-Liang Bi contributed to the overall study design and supervised all research. Shu-Jiu Zhang carried out the experiments and analyzed the data and was also responsible for the final editing of the manuscript. Yi-Zhao Shen contributed partly to the writing and finally revising the manuscript and data analysis. Mirielle Pauline contributed to language editing and revision. Hui Li prepared the figures. He Tang drafted and revised the first version of the manuscript. All the authors reviewed and finally approved the manuscript.

Corresponding author

Correspondence to Chong-Liang Bi.

Ethics declarations

Ethical Approval

All experimental procedures were conducted with the approval of the Institutional Animal Care and Use Committee of Linyi University (Approval ID: [2006], 24).

Conflict of Interest

The authors declare that they have no conflict of interest.

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

Bi, CL., Zhang, SJ., Shen, YZ. et al. Selenium Plays an Anti-Inflammatory Role by Regulation NLRP3 Inflammasome in Staphylococcus aureus-Infected Mouse Mammary Gland. Biol Trace Elem Res 199, 604–610 (2021). https://doi.org/10.1007/s12011-020-02166-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02166-z

Keywords

Navigation