Lymphocytes modulate innate immune responses and neuronal damage in experimental meningitis

Olaf Hoffmann, Olga Rung, Josephin Held, Chotima Boettcher, Stefan Prokop, Werner Stenzel, Josef Priller

Research output: Contribution to journalArticlepeer-review

Abstract

In bacterial meningitis, excessive immune responses carry significant potential for damage to brain tissue even after successful antibiotic therapy. Bacterial meningitis is regarded primarily as the domain of innate immunity, and the role of lymphocytes remains unclear. We studied the contribution of lymphocytes to acute inflammation and neurodegeneration in experimental Toll-like receptor 2-driven meningitis, comparing wild-type mice with RAG-1-deficient mice that have no mature T and B lymphocytes. At 24 h after intrathecal challenge with the synthetic bacterial lipopeptide Pam(3)CysSK(4), RAG-1-deficient mice displayed more pronounced clinical impairment and an increased concentration of neutrophils, reduced expression of interleukin-10 (IL-10) mRNA, and increased expression of CXCL1 mRNA in the cerebrospinal fluid. Conversely, neuronal loss in the dentate gyrus was reduced in RAG-1-deficient mice, and expression of IL-10, transforming growth factor β and CCL2 mRNA by microglia was increased compared to wild-type mice. Adoptive transfer of wild-type lymphocytes reversed the enhanced meningeal inflammation and functional impairment observed in RAG-1-deficient mice. Our findings suggest compartment-specific effects of lymphocytes during acute bacterial meningitis, including attenuation of meningeal inflammation and shifting of microglial activation toward a more neurotoxic phenotype.

Original languageEnglish
Pages (from-to)259-67
Number of pages9
JournalInfection and Immunity
Volume83
Issue number1
DOIs
Publication statusE-pub ahead of print - 27 Oct 2014

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Disease Models, Animal
  • Gene Deletion
  • Gene Expression Profiling
  • Homeodomain Proteins
  • Immunity, Innate
  • Lymphocytes
  • Meningitis, Bacterial
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Journal Article
  • Research Support, Non-U.S. Gov't

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