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	Lea-Jessica Albrecht, Simone C Tauber, Julika Merres, Eugenia Kress, Matthias B Stope, Sandra Jansen, Thomas Pufe, Lars-Ove Brandenburg
Journal	Mediators of inflammation (Mediators Inflamm) Vol. 2016 Pg. 7678542 ( 2016) ISSN: 1466-1861 [Electronic] United States
PMID	27057100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Interleukin-6 Receptors, Tumor Necrosis Factor, Type I
Topics	Animals Immunity, Innate (genetics, immunology) Interleukin-6 (deficiency, genetics) Male Meningitis, Bacterial (immunology, metabolism) Mice Mice, Knockout Pneumococcal Infections (immunology, metabolism) Receptors, Tumor Necrosis Factor, Type I (deficiency, genetics) Streptococcus pneumoniae (immunology, pathogenicity)

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