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 to check access
This study was supported by “The National Key R&D Program of China” (2017YPD0500204).
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.
COMPLIANCE WITH ETHICAL STANDARDS
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
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 was obtained from all individual participants included in the study.
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
Zhang, W., and C.P. Lu. 2007. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 7: 4468–4476.CrossRefPubMedGoogle Scholar
Wertheim, H.F., H.D. Nghia, W. Taylor, and C. Schultsz. 2009. Streptococcus suis: an emerging human pathogen. Clinical Infectious Diseases 48: 617–625.CrossRefPubMedGoogle Scholar
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.PubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefGoogle Scholar
Grenier, D., and C. Bodet. 2008. Streptococcus suis stimulates ICAM-1 shedding from microvascular endothelial cells. FEMS Immunology and Medical Microbiology 54: 271–276.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.PubMedPubMedCentralGoogle Scholar