Skip to main content
SpringerLink
Log in

Immunopathogenesis of Bacterial Meningitis

  • Chapter
  • First Online:
Neuroinflammation and Neurodegeneration

  • 1949 Accesses

Abstract

Despite effective antimicrobial therapy, case-fatality rates and neurologic sequelae of bacterial meningitis remain unacceptably high. Adverse outcomes are related primarily to neurologic complications occurring secondary to meningitis. These complications are mainly a consequence of a hyper-inflammatory reaction to bacterial infection of the subarachnoid space. The harmful inflammatory response is initiated by the recognition of bacterial products through pattern recognition receptors such as toll-like receptors. Their activation leads to a MyD88-dependent production of multiple pro-inflammatory factors like cytokines of the interleukin-1 family or terminal complement products. Subsequently, huge numbers of neutrophils are recruited to the site of infection where they release their antimicrobial arsenal, e.g., oxidants. This can cause collateral damage to brain tissue, resulting in the liberation of endogenous danger molecules. Their presence is also recognized by host pattern recognition receptors and, in consequence, mediates an aggravation and propagation of the hyper-inflammatory response. Based on this knowledge, the most promising targets for adjunctive therapy of bacterial meningitis seem to be limiting the release of bacterial products and interfering with the generation of key pro-inflammatory host factors.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

C:

Complement

CSF:

Cerebrospinal fluid

DAMP:

Danger-associated molecular pattern

HMGB1:

High-mobility group box 1 protein

IL:

Interleukin

LTA:

Lipoteichoic acid

MAC:

Membrane attack complex

MMP:

Matrix metalloproteinase

MyD88:

Myeloid differentiation primary response gene 88 protein

NF:

Nuclear factor

NLR:

NOD-like receptor

NLRP3:

The NLR family, pyrin domain-containing protein 3

NOD:

Nucleotide-binding oligomerization domain

PG:

Peptidoglycan

PLY:

Pneumolysin

PRR:

Pattern recognition receptor

RAGE:

Receptor for advanced glycosylation end products

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

References

  1. World Health Organization. Global Health Observatory: Number of suspected meningitis cases and deaths reported. http://www.who.int/gho/epidemic_diseases/meningitis/suspected_cases_deaths_text/en/2013.

  2. World Health Organization. Epidemic meningococcal disease. WHO Fact Sheet 105, 1998.

    Google Scholar 

  3. Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, Reingold AL, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med. 1997;337:970–6.

    Article  CAS  PubMed  Google Scholar 

  4. Thigpen MC, Whitney CG, Messonnier NE, Zell ER, Lynfield R, Hadler JL, et al. Bacterial meningitis in the United States, 1998–2007. N Engl J Med. 2011;364:2016–25.

    Article  CAS  PubMed  Google Scholar 

  5. De Gans J, Van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347:1549–56.

    Article  PubMed  Google Scholar 

  6. Schmidt H, Heimann B, Djukic M, Mazurek C, Fels C, Wallesch CW, et al. Neuropsychological sequelae of bacterial and viral meningitis. Brain. 2006;129:333–45.

    Article  CAS  PubMed  Google Scholar 

  7. Ramakrishnan M, Ulland AJ, Steinhardt LC, Moisi JC, Were F, Levine OS. Sequelae due to bacterial meningitis among African children: a systematic literature review. BMC Med. 2009;7:47.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Kastenbauer S, Pfister HW. Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain. 2003;126:1015–25.

    Article  PubMed  Google Scholar 

  9. Van de Beek D, De Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004;351:1849–59.

    Article  PubMed  Google Scholar 

  10. Katchanov J, Siebert E, Endres M, Klingebiel R. Focal parenchymal lesions in community-acquired bacterial meningitis in adults: a clinico-radiological study. Neuroradiology. 2009;51: 723–9.

    Article  PubMed  Google Scholar 

  11. Pfister HW, Feiden W, Einhäupl KM. Spectrum of complications during bacterial meningitis in adults. Arch Neurol. 1993;505:575–81.

    Article  Google Scholar 

  12. Schut ES, Lucas MJ, Brouwer MC, Vergouwen MD, van der Ende A, van de Beek D. Cerebral infarction in adults with bacterial meningitis. Neurocrit Care. 2011;16:421–7.

    Article  Google Scholar 

  13. Perry FE, Elson CJ, Greenham LW, Catterall JR. Interference with the oxidative response of neutrophils by Streptococcus pneumoniae. Thorax. 1993;48:364–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Brouwer MC, McIntyre P, de Gans J, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2010;9, CD004405.

    PubMed  Google Scholar 

  15. Van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR. Advances in treatment of bacterial meningitis. Lancet. 2012;380:1693–702.

    Article  PubMed  Google Scholar 

  16. Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res. 2004;1:2.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Dujardin BC, Driedijk PC, Roijers AF, Out TA. The determination of the complement components C1q, C4 and C3 in serum and cerebrospinal fluid by radioimmunoassay. J Immunol Methods. 1985;80:227–37.

    Article  CAS  PubMed  Google Scholar 

  18. Stahel PF, Nadal D, Pfister HW, Paradisis PM, Barnum SR. Complement C3 and factor B cerebrospinal fluid concentrations in bacterial and aseptic meningitis. Lancet. 1997;349: 1886–7.

    Article  CAS  PubMed  Google Scholar 

  19. Pachter JS, De Vries HE, Fabry Z. The blood-brain barrier and its role in immune privilege in the central nervous system. J Neuropathol Exp Neurol. 2003;62:593–604.

    CAS  PubMed  Google Scholar 

  20. Smith H, Bannister B, O’Shea MJ. Cerebrospinal fluid immunoglobulins in meningitis. Lancet. 1977;2:591–3.

    Google Scholar 

  21. Pashenkov M, Link H. Dendritic cells and immune responses in the central nervous system. Trends Immunol. 2002;23:69–70.

    Article  CAS  PubMed  Google Scholar 

  22. Guillemin GJ, Brew BJ. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol. 2004;75:388–97.

    Article  CAS  PubMed  Google Scholar 

  23. Niederkorn JY. See no evil, hear no evil, do no evil: the lessons of immune privilege. Nat Immunol. 2006;7:354–9.

    Article  CAS  PubMed  Google Scholar 

  24. Gordon LB, Nolan SC, Ksander BR, Knopf PM, Harling-Berg CJ. Normal cerebrospinal fluid suppresses the in vitro development of cytotoxic T cells: role of the brain microenvironment in CNS immune regulation. J Neuroimmunol. 1998;88:77–84.

    Article  CAS  PubMed  Google Scholar 

  25. Nagai A, Terashima M, Sheikh AM, Notsu Y, Shimode K, Yamaguchi S, et al. Involvement of cystatin C in pathophysiology of CNS diseases. Front Biosci. 2008;13:3470–9.

    Article  CAS  PubMed  Google Scholar 

  26. Hoffmann O, Priller J, Prozorovski T, Schulze-Topphoff U, Baeva N, Lunemann JD, et al. TRAIL limits excessive host immune responses in bacterial meningitis. J Clin Invest. 2007;117:2004–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Small PM, Tauber MG, Hackbarth CJ, Sande MA. Influence of body temperature on bacterial growth rates in experimental pneumococcal meningitis in rabbits. Infect Immun. 1986;52:484–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Tuomanen E, Tomasz A, Hengstler B, Zak O. The relative role of bacterial cell wall and capsule in the induction of inflammation in pneumococcal meningitis. J Infect Dis. 1985;151: 535–40.

    Article  CAS  PubMed  Google Scholar 

  29. Tuomanen E, Hengstler B, Zak O, Tomasz A. Induction of meningeal inflammation by diverse bacterial cell walls. Eur J Clin Microbiol. 1986;5:682–4.

    Article  CAS  PubMed  Google Scholar 

  30. Tuomanen EI, Saukkonen K, Sande S, Cioffe C, Wright SD. Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. J Exp Med. 1989;170:959–69.

    Article  CAS  PubMed  Google Scholar 

  31. Schneider O, Michel U, Zysk G, Dubuis O, Nau R. Clinical outcome in pneumococcal meningitis correlates with CSF lipoteichoic acid concentrations. Neurology. 1999;53:1584–7.

    Article  CAS  PubMed  Google Scholar 

  32. Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol. 1999;163:1–5.

    CAS  PubMed  Google Scholar 

  33. Koedel U, Angele B, Rupprecht T, Wagner H, Roggenkamp A, Pfister HW, et al. Toll-like receptor 2 participates in mediation of immune response in experimental pneumococcal meningitis. J Immunol. 2003;170:438–44.

    Article  CAS  PubMed  Google Scholar 

  34. Schroder NW, Morath S, Alexander C, Hamann L, Hartung T, Zahringer U, et al. Lipoteichoic acid (LTA) of S. pneumoniae and S. aureus activates immune cells via toll-like receptor (TLR)-2, LPS binding protein (LBP) and CD14 while TLR-4 and MD-2 are not involved. J Biol Chem. 2003;278:15587–94.

    Article  PubMed  Google Scholar 

  35. Malley R, Henneke P, Morse SC, Cieslewicz MJ, Lipsitch M, Thompson CM, et al. Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc Natl Acad Sci U S A. 2003;100:1966–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Shoma S, Tsuchiya K, Kawamura I, Nomura T, Hara H, Uchiyama R, et al. Critical involvement of pneumolysin in production of IL-1α and caspase-1-dependent cytokines in infection with Streptococcus pneumoniae in vitro: a novel function of pneumolysin in caspase-1 activation. Infect Immun. 2008;76:1547–57.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. McNeela EA, Burke A, Neill DR, Baxter C, Fernandes VE, Ferreira D, et al. Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4. PLoS Pathog. 2010;6:e1001191.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Witzenrath M, Pache F, Lorenz D, Koppe U, Gutbier B, Tabeling C, et al. The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia. J Immunol. 2011;187:434–40.

    Article  CAS  PubMed  Google Scholar 

  39. Mogensen TH, Paludan SR, Kilian M, Ostergaard L. Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response through Toll-like receptors 2, 4, and 9 in species-specific patterns. J Leukoc Biol. 2006;80:267–77.

    Article  CAS  PubMed  Google Scholar 

  40. Oldenburg M, Kruger A, Ferstl R, Kaufmann A, Nees G, Sigmund A, et al. TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science. 2012;337:1111–5.

    Article  CAS  PubMed  Google Scholar 

  41. Klein M, Angele B, Pfister HW, Wagner H, Koedel U, Kirschning CJ. Detection of pneumococcal infection of the central nervous system depends upon TLR2 and TLR4. J Infect Dis. 2008;198:1028–36.

    Article  CAS  PubMed  Google Scholar 

  42. Opitz B, Puschel A, Schmeck B, Hocke AC, Rosseau S, Hammerschmidt S, et al. Nucleotide-binding oligomerization domain proteins are innate immune receptors for internalized Streptococcus pneumoniae. J Biol Chem. 2004;279:36426–32.

    Article  CAS  PubMed  Google Scholar 

  43. Liu X, Chauhan VS, Young AB, Marriott I. NOD2 mediates inflammatory responses of primary murine glia to Streptococcus pneumoniae. Glia. 2010;58:839–47.

    PubMed Central  PubMed  Google Scholar 

  44. Hoegen T, Tremel N, Klein M, Angele B, Wagner H, Kirschning C, et al. The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release. J Immunol. 2011;187:5440–51.

    Article  CAS  PubMed  Google Scholar 

  45. Koedel U, Rupprecht T, Angele B, Heesemann J, Wagner H, Pfister HW, et al. MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS. Brain. 2004;127:1437–45.

    Article  PubMed  Google Scholar 

  46. Brouwer MC, de Gans J, Heckenberg SG, Zwinderman AH, van der Poll T, van de Beek D. Host genetic susceptibility to pneumococcal and meningococcal disease: a systematic review and meta-analysis. Lancet Infect Dis. 2009;9:31–44.

    Article  CAS  PubMed  Google Scholar 

  47. Bogaert D, Thompson CM, Trzcinski K, Malley R, Lipsitch M. The role of complement in innate and adaptive immunity to pneumococcal colonization and sepsis in a murine model. Vaccine. 2010;28:681–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Rupprecht TA, Angele B, Klein M, Heesemann J, Pfister HW, Botto M, et al. Complement C1q and C3 are critical for the innate immune response to Streptococcus pneumoniae in the central nervous system. J Immunol. 2007;178:1861–9.

    Article  CAS  PubMed  Google Scholar 

  49. Koedel U, Bayerlein I, Paul R, Sporer B, Pfister HW. Pharmacological interference with NF-B activation attenuates central nervous system complications in experimental pneumococcal meningitis. J Infect Dis. 2000;182:1437–45.

    Article  CAS  PubMed  Google Scholar 

  50. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–50.

    Article  CAS  PubMed  Google Scholar 

  51. Mustafa MM, Lebel MH, Ramilo O, Olsen KD, Reisch JS, Beutler B, et al. Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr. 1989;115:208–13.

    Article  CAS  PubMed  Google Scholar 

  52. Fassbender K, Mielke O, Bertsch T, Muehlhauser F, Hennerici M, Kurimoto M, et al. Interferon-gamma-inducing factor (IL-18) and interferon-gamma in inflammatory CNS diseases. Neurology. 1999;53:1104–6.

    Article  CAS  PubMed  Google Scholar 

  53. Quagliarello VJ, Wispelwey B, Long WJJ, Scheld WM. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. J Clin Invest. 1991;87:1360–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Ramilo O, Saez-Llorens X, Mertsola J, Jafari H, Olsen KD, Hansen EJ, et al. Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. J Exp Med. 1990;172:497–507.

    Article  CAS  PubMed  Google Scholar 

  55. Saukkonen K, Sande S, Cioffe C, Wolpe S, Sherrry B, Cerami A, et al. The role of cytokines in the generation of inflammation and tissue damage in experimental pneumococcal meningitis. J Exp Med. 1990;171:439–48.

    Article  CAS  PubMed  Google Scholar 

  56. Zwijnenburg PJ, Van der Poll T, Florquin S, Roord JJ, Van Furth AM. IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis. J Immunol. 2003;170:4724–30.

    Article  CAS  PubMed  Google Scholar 

  57. Zwijnenburg PJ, Van der Poll T, Florquin S, Akira S, Takeda K, Roord JJ, et al. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis. J Neuroimmunol. 2003;138:31–7.

    Article  CAS  PubMed  Google Scholar 

  58. Koedel U, Winkler F, Angele B, Fontana A, Flavell RA, Pfister HW. Role of caspase-1 in experimental pneumococcal meningitis: evidence from pharmacologic caspase inhibition and caspase-1-deficient mice. Ann Neurol. 2002;51:319–29.

    Article  CAS  PubMed  Google Scholar 

  59. Braun JS, Novak R, Herzog K-H, Bodner SM, Cleveland JL, Tuomanen EI. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat Med. 1999;5:298–302.

    Article  CAS  PubMed  Google Scholar 

  60. Woehrl B, Brouwer MC, Murr C, Heckenberg SG, Baas F, Pfister HW, et al. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis. J Clin Invest. 2011;121:3943–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Ehrnthaller C, Ignatius A, Gebhard F, Huber-Lang M. New insights of an old defense system: structure, function, and clinical relevance of the complement system. Mol Med. 2011;17:317–29.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Trouw LA, Daha MR. Role of complement in innate immunity and host defense. Immunol Lett. 2011;138:35–7.

    Article  CAS  PubMed  Google Scholar 

  63. Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Kohl J. The role of the anaphylatoxins in health and disease. Mol Immunol. 2009;46:2753–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Woodruff TM, Nandakumar KS, Tedesco F. Inhibiting the C5-C5a receptor axis. Mol Immunol. 2011;48:1631–42.

    Article  CAS  PubMed  Google Scholar 

  65. Kadurugamuwa JL, Hengstler B, Bray MA, Zak O. Inhibition of complement-factor-C5a-induced inflammatory reactions by prostaglandin E2 in experimental meningitis. J Infect Dis. 1989;160:715–9.

    Article  CAS  PubMed  Google Scholar 

  66. Casarsa C, De Luigi A, Pausa M, De Simoni MG, Tedesco F. Intracerebroventricular injection of the terminal complement complex causes inflammatory reaction in the rat brain. Eur J Immunol. 2003;33:1260–70.

    Article  CAS  PubMed  Google Scholar 

  67. Ernst JD, Hartiala KT, Goldstein IM, Sande MA. Complement (C5)-derived chemotactic activity accounts for accumulation of polymorphonuclear leukocytes in cerebrospinal fluid of rabbits with pneumococcal meningitis. Infect Immun. 1984;46:81–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Matzinger P. Friendly and dangerous signals: is the tissue in control? Nat Immunol. 2007;8:11–3.

    Article  CAS  PubMed  Google Scholar 

  69. Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008;8:279–89.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81:1–5.

    Article  CAS  PubMed  Google Scholar 

  71. Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011;29:139–62.

    Article  CAS  PubMed  Google Scholar 

  72. Lamkanfi M, Sarkar A, Vande WL, Vitari AC, Amer AO, Wewers MD, et al. Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. J Immunol. 2010;185:4385–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Bianchi ME. HMGB1 loves company. J Leukoc Biol. 2009;86:573–6.

    Article  CAS  PubMed  Google Scholar 

  74. Harris HE, Andersson U, Pisetsky DS. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol. 2012;8:195–202.

    Article  CAS  PubMed  Google Scholar 

  75. Tang D, Kang R, Cao L, Zhang G, Yu Y, Xiao W, et al. A pilot study to detect high mobility group box 1 and heat shock protein 72 in cerebrospinal fluid of pediatric patients with meningitis. Crit Care Med. 2008;36:291–5.

    Article  CAS  PubMed  Google Scholar 

  76. Asano T, Ichiki K, Koizumi S, Kaizu K, Hatori T, Mashiko K, et al. High mobility group box 1 in cerebrospinal fluid from several neurological diseases at early time points. Int J Neurosci. 2011;121:480–4.

    Article  PubMed  Google Scholar 

  77. Höhne C, Wenzel M, Angele B, Hammerschmidt S, Häcker H, Klein M, et al. High mobility group box 1 prolongs inflammation and worsens disease in pneumococcal meningitis. Brain. 2013. doi:10.1093/brain/awt064.

    PubMed  Google Scholar 

  78. Blazer S, Berant M, Alon U. Bacterial meningitis. Effect of antibiotic treatment on cerebrospinal fluid. Am J Clin Pathol. 1983;80:386–7.

    CAS  PubMed  Google Scholar 

  79. Viallon A, Guyomarc’h P, Guyomarc’h S, Tardy B, Robert F, Marjollet O, et al. Decrease in serum procalcitonin levels over time during treatment of acute bacterial meningitis. Crit Care. 2005;9:R344–50.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics. 2001;108:1169–74.

    CAS  PubMed  Google Scholar 

  81. Gerber J, Pohl K, Sander V, Bunkowski S, Nau R. Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone. Antimicrob Agents Chemother. 2003;47:1313–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Stucki A, Cottagnoud M, Winkelmann V, Schaffner T, Cottagnoud P. Daptomycin produces an enhanced bactericidal activity compared to ceftriaxone, measured by [3H]choline release in the cerebrospinal fluid, in experimental meningitis due to a penicillin-resistant pneumococcal strain without lysing its cell wall. Antimicrob Agents Chemother. 2007;51:2249–52.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Koedel U, Frankenberg T, Kirschnek S, Obermaier B, Hacker H, Paul R, et al. Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis. PLoS Pathog. 2009;5:e1000461.

    Article  PubMed Central  PubMed  Google Scholar 

  84. Klein M, Koedel U, Pfister HW. Oxidative stress in pneumococcal meningitis: a future target for adjunctive therapy? Prog Neurobiol. 2006;80:269–80.

    Article  CAS  PubMed  Google Scholar 

  85. Kastenbauer S, Koedel U, Becker BF, Pfister HW. Oxidative stress in bacterial meningitis in humans. Neurology. 2002;58:186–91.

    Article  CAS  PubMed  Google Scholar 

  86. Rosenberg GA. Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol. 2009;8:205–16.

    Article  CAS  PubMed  Google Scholar 

  87. Leppert D, Lindberg RL, Kappos L, Leib SL. Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis. Brain Res Brain Res Rev. 2001;36:249–57.

    Article  CAS  PubMed  Google Scholar 

  88. Woehrl B, Klein M, Grandgirard D, Koedel U, Leib S. Bacterial meningitis: current therapy and possible future treatment options. Expert Rev Anti Infect Ther. 2011;9:1053–65.

    Article  CAS  PubMed  Google Scholar 

  89. Straus SK, Hancock RE. Mode of action of the new antibiotic for Gram-positive pathogens daptomycin: comparison with cationic antimicrobial peptides and lipopeptides. Biochim Biophys Acta. 2006;1758:1215–23.

    Article  CAS  PubMed  Google Scholar 

  90. Egermann U, Stanga Z, Ramin A, Acosta F, Stucki A, Gerber P, et al. Combination of daptomycin plus ceftriaxone is more active than vancomycin plus ceftriaxone in experimental meningitis after addition of dexamethasone. Antimicrob Agents Chemother. 2009;53:3030–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Mook-Kanamori BB, Rouse MS, Kang CI, van de Beek D, Steckelberg JM, Patel R. Daptomycin in experimental murine pneumococcal meningitis. BMC Infect Dis. 2009;9:50.

    Article  PubMed Central  PubMed  Google Scholar 

  92. Grandgirard D, Schurch C, Cottagnoud P, Leib SL. Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother. 2007;51:2173–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Grandgirard D, Oberson K, Buhlmann A, Gaumann R, Leib SL. Attenuation of cerebrospinal fluid inflammation by the non-bacteriolytic antibiotic daptomycin vs. ceftriaxone in experimental pneumococcal meningitis. Antimicrob Agents Chemother. 2010;54:1323–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Ramos TN, Wohler JE, Barnum SR. Deletion of both the C3a and C5a receptors fails to protect against experimental autoimmune encephalomyelitis. Neurosci Lett. 2009;467:234–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Kullar R, Chin JN, Edwards DJ, Parker D, Coplin WM, Rybak MJ. Pharmacokinetics of single-dose daptomycin in patients with suspected or confirmed neurological infections. Antimicrob Agents Chemother. 2011;55:3505–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgment

The authors’ research is funded by the German Research Foundation, the German Ministry for Research and Education, the Else Kroener-Fresenius-Foundation, the Research and Education Program of the University of Munich, and Novartis Pharmaceuticals.

Author information

Authors and Affiliations

  1. Department of Neurology, University Clinic of Grosshadern, Ludwig-Maximilians-University, Marchioninistr. 15, Munich, 81377, Germany

    Uwe Koedel, Matthias Klein & Hans-Walter Pfister

Authors
  1. Uwe Koedel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans-Walter Pfister
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uwe Koedel .

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    Phillip K. Peterson

  2. Department of Biochemistry Department of Molecular Biology, University of Miami School of Medicine, Miami, Florida, USA

    Michal Toborek

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Koedel, U., Klein, M., Pfister, HW. (2014). Immunopathogenesis of Bacterial Meningitis. In: Peterson, P., Toborek, M. (eds) Neuroinflammation and Neurodegeneration. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1071-7_18

Download citation

Publish with us

Policies and ethics

Search

Navigation