Journal
PLOS ONE
Volume 9, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0093057
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Funding
- Meningitis Research Foundation (MRF)
- Deutsche Forschungsgemeinschaft (DFG)
- University of Munich
- Friedrich Baur Stiftung
- Else Kroener Fresenius Foundation (EKFS)
- American Lebanese Syrian Associated Charities (ALSAC)
- Netherlands Organization for Health Research and Development (ZonMw NWO-Veni) [916.76.023]
- Netherlands Organization for Health Research and Development (ZonMw NWO406 Vidi) [917.11.358]
- Academic Medical Center (AMC)
- European Research Council (ERC) [281156]
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We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6 deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.
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