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TRAIL limits excessive host immune responses in bacterial meningitis

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Official URL:https://doi.org/10.1172/JCI30356
PubMed:View item in PubMed
Creators Name:Hoffmann, O. and Priller, J. and Prozorovski, T. and Schulze-Topphoff, U. and Baeva, N. and Lunemann, J.D. and Aktas, O. and Mahrhofer, C. and Stricker, S. and Zipp, F. and Weber, J.R.
Journal Title:Journal of Clinical Investigation
Journal Abbreviation:J Clin Invest
Volume:117
Number:7
Page Range:2004-2013
Date:2 July 2007
Keywords:Antigens, CD18, Cell Survival, Cytokines, Gene Expression Regulation, Genotype, Gram-Positive Cocci, Granulocytes, Hippocampus, Leukocytes, Bacterial Meningitis, Neisseria, Recombinant Proteins, Solubility, Survival Rate, Animals, Mice
Abstract:Apart from potential roles in anti-tumor surveillance, the TNF-related apoptosis-inducing ligand (TRAIL) has important regulatory functions in the host immune response. We studied antiinflammatory effects of endogenous and recombinant TRAIL (rTRAIL) in experimental meningitis. Following intrathecal application of pneumococcal cell wall, a TLR2 ligand, we found prolonged inflammation, augmented clinical impairment, and increased apoptosis in the hippocampus of TRAIL(-/-) mice. Administration of rTRAIL into the subarachnoid space of TRAIL(-/-) mice or reconstitution of hematopoiesis with wild-type bone marrow cells reversed these effects, suggesting an autoregulatory role of TRAIL within the infiltrating leukocyte population. Importantly, intrathecal application of rTRAIL in wild-type mice with meningitis also decreased inflammation and apoptosis. Moreover, patients suffering from bacterial meningitis showed increased intrathecal synthesis of TRAIL. Our findings provide what we believe is the first evidence that TRAIL may act as a negative regulator of acute CNS inflammation. The ability of TRAIL to modify inflammatory responses and to reduce neuronal cell death in meningitis suggests that it may be used as a novel antiinflammatory agent in invasive infections.
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Additional Information:Articles from The Journal of Clinical Investigation are provided here courtesy of the American Society for Clinical Investigation.
Item Type:Article

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