title: Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis.
abstract: The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6(-/-), TNFR1(-/-), and TNFR1-IL-6(-/-) KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1(-/-), IL-6(-/-), and TNFR1-IL-6(-/-) mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1(-/-) and TNFR1-IL-6(-/-) mice in contrast to IL-6(-/-) and wild type mice. Furthermore, the increased mortality of TNFR1(-/-) and TNFR1-IL-6(-/-) mice correlated with decreased glial cell activation compared to IL-6(-/-) or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Lea-Jessica
authors.initials: LJ
authors.lastname: Albrecht
authors.affiliation: Department of Neurology, RWTH University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Simone C
authors.initials: SC
authors.lastname: Tauber
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Julika
authors.initials: J
authors.lastname: Merres
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kress
authors.affiliation: Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jansen
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Lars-Ove
authors.initials: LO
authors.lastname: Brandenburg
mesh_terms: D000818:Animals; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D016920:Meningitis, Bacterial / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011008:Pneumococcal Infections / Q000276:immunology* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency* / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity
chemical_list: D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I