Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis
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 s...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/7678542 |
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| author | Lea-Jessica Albrecht Simone C. Tauber Julika Merres Eugenia Kress Matthias B. Stope Sandra Jansen Thomas Pufe Lars-Ove Brandenburg |
| author_facet | Lea-Jessica Albrecht Simone C. Tauber Julika Merres Eugenia Kress Matthias B. Stope Sandra Jansen Thomas Pufe Lars-Ove Brandenburg |
| author_sort | Lea-Jessica Albrecht |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3c5ff74382bd4bba9bcd5de1c67cc513 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-3c5ff74382bd4bba9bcd5de1c67cc5132025-02-03T06:07:51ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/76785427678542Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial MeningitisLea-Jessica Albrecht0Simone C. Tauber1Julika Merres2Eugenia Kress3Matthias B. Stope4Sandra Jansen5Thomas Pufe6Lars-Ove Brandenburg7Department of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Neurology, RWTH University Hospital Aachen, 52074 Aachen, GermanyDepartment of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Urology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Anatomy and Cell Biology, RWTH Aachen University, 52074 Aachen, GermanyThe 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.http://dx.doi.org/10.1155/2016/7678542 |
| spellingShingle | Lea-Jessica Albrecht Simone C. Tauber Julika Merres Eugenia Kress Matthias B. Stope Sandra Jansen Thomas Pufe Lars-Ove Brandenburg Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis Mediators of Inflammation |
| 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 |
| title_full | Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis |
| title_fullStr | Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis |
| title_full_unstemmed | Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis |
| title_short | Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis |
| title_sort | lack of proinflammatory cytokine interleukin 6 or tumor necrosis factor receptor 1 results in a failure of the innate immune response after bacterial meningitis |
| url | http://dx.doi.org/10.1155/2016/7678542 |
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