PLoS ONE (Jan 2014)

Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis.

  • Matthias Klein,
  • Matthijs C Brouwer,
  • Barbara Angele,
  • Madelijn Geldhoff,
  • Gabriel Marquez,
  • Rosa Varona,
  • Georg Häcker,
  • Helga Schmetzer,
  • Hans Häcker,
  • Sven Hammerschmidt,
  • Arie van der Ende,
  • Hans-Walter Pfister,
  • Diederik van de Beek,
  • Uwe Koedel

DOI
https://doi.org/10.1371/journal.pone.0093057
Journal volume & issue
Vol. 9, no. 4
p. e93057

Abstract

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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.