Skip to main content

Advertisement

SpringerLink
Log in

Characteristic Comparison of Meningitis and Non-meningitis of Streptococcus suis in an Experimentally Infected Porcine Model

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

This study tested the differences of meningitis and non-meningitis of Streptococcus suis (SS). In this study, an infected pig model of streptococcal meningitis was established. Compared with the non-meningitis Streptococcus suis group (JZLQ001 group), the meningitis Streptococcus suis group (JZLQ022) exhibited neurological symptoms, such as ataxia and foaming at the mouth, and the brain showed a large area of congestion at 5 days post-infection (p.i.). Moreover, bacterial counts, white blood cells (WBCs), neutrophils, and blood glucose in the blood reached a peak and were significantly higher than those of the JZLQ001 group at 3 days p.i. These values then decreased at 5 days p.i. However, the content of total protein in the blood was lower in the JZLQ022 group than that in the JZLQ001 group, and the difference was most significant at 5 days p.i. When neurological symptoms appeared on 5 days p.i., the bacterial counts in the brain in the JZLQ022 group were significantly higher than those in the JZLQ001 group. The levels of cytokines in the peripheral blood and cerebrospinal fluid (CSF) were an important indicator of inflammation. By ELISA detection, the secretion levels of IL-6, IL-8, and IL-17 in the peripheral blood in the JZLQ022 group were significantly higher than those in the JZLQ001 group at 12 and 24 h and 3 days p.i.; however, TNF-α showed no difference. At 5 days p.i., the secretion levels of IL-6, IL-8, and IL-17 in the JZLQ022 group were significantly lower than those in the JZLQ001 group. The results were similar in CSF. HE staining revealed that the JZLQ022 group exhibited neuronophagia and hyperemia in the brain, but no change was found in the JZLQ001 group. A further study investigating the impact of meningitis Streptococcus suis on blood-brain barrier (BBB) integrity found that the brain tissue content of endogenous IgG in the JZLQ022 group was significantly higher than that in the JZLQ001 group. The present study demonstrated that pigs infected with meningitis and non-meningitis Streptococcus suis exhibit significant differences in immunological aspects such as bacterial counts, WBCs, neutrophils, blood glucose and total protein in the peripheral blood, the secretion levels of IL-6, IL-8, and IL-17, and BBB integrity. These data provide the necessary evidence to better understand SS meningitis.

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

Access this article

Log in via an institution

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
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

SS:

Streptococcus suis

MCP:

Monocyte chemotaxis proteins

CSF:

Cerebrospinal fluid

WBCs:

White blood cells

PBS:

Phosphate-buffered saline

BBB:

Blood-brain barrier

REFERENCES

  1. Madsen, L.W., B. Svensmark, K. Elvestad, B. Aalbaek, and H.E. Jensen. 2002. Streptococcus suis serotype 2 infection in pigs: new diagnostic and pathogenetic aspects. Journal of Comparative Pathology 126: 57–65.

    Article  CAS  PubMed  Google Scholar 

  2. Beineke, A., K. Bennecke, C. Neis, C. Schroder, K.H. Waldmann, W. Baumgartner, et al. 2008. Comparative evaluation of virulence and pathology of Streptococcus suis serotypes 2 and 9 in experimentally infected growers. Veterinary Microbiology 128: 423–430.

    Article  PubMed  Google Scholar 

  3. Yu, H., H. Jing, Z. Chen, H. Zheng, X. Zhu, H. Wang, et al. 2006. Human Streptococcus suis outbreak, Sichuan, China. Emerging Infectious Diseases 12: 914–920.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhang, W., and C.P. Lu. 2007. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 7: 4468–4476.

    Article  CAS  PubMed  Google Scholar 

  5. Wertheim, H.F., H.D. Nghia, W. Taylor, and C. Schultsz. 2009. Streptococcus suis: an emerging human pathogen. Clinical Infectious Diseases 48: 617–625.

    Article  PubMed  Google Scholar 

  6. Huong, V.T., N. Ha, N.T. Huy, P. Horby, H.D. Nghia, V.D. Thiem, et al. 2014. Epidemiology, clinical manifestations, and outcomes of Streptococcus suis infection in humans. Emerging Infectious Diseases 20: 1105–1114.

    PubMed  PubMed Central  Google Scholar 

  7. Praphasiri, P., J.T. Owusu, S. Thammathitiwat, D. Ditsungnoen, P. Boonmongkon, O. Sangwichian, et al. 2015. Streptococcus suis infection in hospitalized patients, Nakhon Phanom Province, Thailand. Emerging Infectious Diseases 21: 345–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu, M., L. Fang, C. Tan, T. Long, H. Chen, and S. Xiao. 2011. Understanding Streptococcus suis serotype 2 infection in pigs through a transcriptional approach. BMC Genomics 12: 253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dominguez-Punaro, M.C., M. Segura, M.M. Plante, S. Lacouture, S. Rivest, and M. Gottschalk. 2007. Streptococcus suis serotype 2, an important swine and human pathogen, induces strong systemic and cerebral inflammatory responses in a mouse model of infection. Journal of Immunology 179: 1842–1854.

    Article  CAS  Google Scholar 

  10. Prasad, R., R. Kapoor, R. Srivastava, O.P. Mishra, and T.B. Singh. 2014. Cerebrospinal fluid TNF-alpha, IL-6, and IL-8 in children with bacterial meningitis. Pediatric Neurology 50: 60–65.

    Article  PubMed  Google Scholar 

  11. Pinto, J.V., M.C. Rebelo, R.N. Gomes, E.F. Assis, H.C. Castro-Faria-Neto, and M.N. Boia. 2011. IL-6 and IL-8 in cerebrospinal fluid from patients with aseptic meningitis and bacterial meningitis: their potential role as a marker for differential diagnosis. The Brazilian Journal of Infectious Diseases 15: 156–158.

    Article  CAS  Google Scholar 

  12. Grenier, D., and C. Bodet. 2008. Streptococcus suis stimulates ICAM-1 shedding from microvascular endothelial cells. FEMS Immunology and Medical Microbiology 54: 271–276.

    Article  CAS  PubMed  Google Scholar 

  13. Al-Numani, D., M. Segura, M. Dore, and M. Gottschalk. 2003. Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2. Clinical and Experimental Immunology 133: 67–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Banerjee, A., B.J. Kim, E.M. Carmona, A.S. Cutting, M.A. Gurney, C. Carlos, et al. 2011. Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration. Nature Communications 2: 462.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Utepbergenov, D.I., K. Mertsch, A. Sporbert, K. Tenz, M. Paul, R.F. Haseloff, et al. 1998. Nitric oxide protects blood-brain barrier in vitro from hypoxia/reoxygenation-mediated injury. FEBS Letters 424: 197–201.

    Article  CAS  PubMed  Google Scholar 

  16. Vivas, M., E. Force, F. Tubau, H.C. El, J. Ariza, and C. Cabellos. 2015. Effect of dexamethasone on the efficacy of daptomycin in the therapy of experimental pneumococcal meningitis. International Journal of Antimicrobial Agents 46: 28–32.

    Article  CAS  PubMed  Google Scholar 

  17. Koedel, U., and H.W. Pfister. 1999. Models of experimental bacterial meningitis. Role and limitations. Infectious Disease Clinics of North America 13 (549–77): vi.

    Google Scholar 

  18. de Greeff, A., S. van Selm, H. Buys, J.F. Harders-Westerveen, R.N. Tunjungputri, Q. de Mast, et al. 2016. Pneumococcal colonization and invasive disease studied in a porcine model. BMC Microbiology 16: 102.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bi, Y., J. Li, L. Yang, S. Zhang, Y. Li, X. Jia, et al. 2014. Assessment of the pathogenesis of Streptococcus suis type 2 infection in piglets for understanding streptococcal toxic shock-like syndrome, meningitis, and sequelae. Veterinary Microbiology 173: 299–309.

    Article  CAS  PubMed  Google Scholar 

  20. Vecht, U., N. Stockhofe-Zurwieden, B.J. Tetenburg, H.J. Wisselink, and H.E. Smith. 1997. Virulence of Streptococcus suis type 2 for mice and pigs appeared host-specific. Veterinary Microbiology 58: 53–60.

    Article  CAS  PubMed  Google Scholar 

  21. Greenlee-Wacker, M.C., and W.M. Nauseef. 2017. IFN-gamma targets macrophage-mediated immune responses toward Staphylococcus aureus. Journal of Leukocyte Biology 101 (3): 751–758.

  22. Doran, K.S., G.Y. Liu, and V. Nizet. 2003. Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis. The Journal of Clinical Investigation 112: 736–744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Asano, T., K. Ichiki, S. Koizumi, K. Kaizu, T. Hatori, O. Fujino, et al. 2010. IL-17 is elevated in cerebrospinal fluids in bacterial meningitis in children. Cytokine 51: 101–106.

    Article  CAS  PubMed  Google Scholar 

  24. Bociaga-Jasik, M., A. Garlicki, A. Ciesla, A. Kalinowska-Nowak, I. Sobczyk-Krupiarz, and T. Mach. 2012. The diagnostic value of cytokine and nitric oxide concentrations in cerebrospinal fluid for the differential diagnosis of meningitis. Advances in Medical Sciences 57: 142–147.

    Article  CAS  PubMed  Google Scholar 

  25. van Sorge, N.M., C.M. Ebrahimi, S.M. McGillivray, D. Quach, M. Sabet, D.G. Guiney, et al. 2008. Anthrax toxins inhibit neutrophil signaling pathways in brain endothelium and contribute to the pathogenesis of meningitis. PLoS One 3: e2964.

    Article  PubMed  PubMed Central  Google Scholar 

  26. La Scolea, L.J., and D. Dryja. 1984. Quantitation of bacteria in cerebrospinal fluid and blood of children with meningitis and its diagnostic significance. Journal of Clinical Microbiology 19: 187–190.

    PubMed  PubMed Central  Google Scholar 

Download references

ACKNOWLEDGEMENTS

This study was supported by “The National Key R&D Program of China” (2017YPD0500204).

Author information

Authors and Affiliations

  1. College of Veterinary Medicine, Jilin University, Xi’an Road 5333, Changchun, 130062, People’s Republic of China

    Yingying Sun, Hongtao Liu, Rining Zhu, Shuang Zhao, Jingmin Gu, Changjiang Sun, Xin Feng, Wenyu Han & Liancheng Lei

  2. College of Chinese Medicine Material, Jilin Agricultural University, Changchun, People’s Republic of China

    Rui Du

  3. Shandong Binzhou Animal Science and Veterinary Medicine Academy, Binzhou, People’s Republic of China

    Shuguang Li & Guanggang Qu

Authors
  1. Yingying Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongtao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shuguang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guanggang Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rining Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shuang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jingmin Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Changjiang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xin Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Wenyu Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Liancheng Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YS and LL conceived and designed the experiments. YS, HL, RD, SL, GQ, and RZ performed the experiments. YS analyzed the data. SZ, JG, CS, XF, and WH contributed reagents/materials/analysis tools. YS contributed to the writing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Liancheng Lei.

Ethics declarations

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

ETHICAL APPROVAL

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The protocol was reviewed by the Institutional Animal Care and the Committee of Jilin University under the approved protocol number JLUA-1309.

INFORMED CONSENT

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, Y., Liu, H., Du, R. et al. Characteristic Comparison of Meningitis and Non-meningitis of Streptococcus suis in an Experimentally Infected Porcine Model. Inflammation 41, 368–377 (2018). https://doi.org/10.1007/s10753-017-0692-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-017-0692-4

KEY WORDS

Search

Navigation