TY - JOUR
T1 - Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis
AU - Klein, Matthias
AU - Brouwer, Matthijs C.
AU - Angele, Barbara
AU - Geldhoff, Madelijn
AU - Marquez, Gabriel
AU - Varona, Rosa
AU - Häcker, Georg
AU - Schmetzer, Helga
AU - Häcker, Hans
AU - Hammerschmidt, Sven
AU - van der Ende, Arie
AU - Pfister, Hans-Walter
AU - van de Beek, Diederik
AU - Koedel, Uwe
PY - 2014
Y1 - 2014
N2 - 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
AB - 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
U2 - https://doi.org/10.1371/journal.pone.0093057
DO - https://doi.org/10.1371/journal.pone.0093057
M3 - Article
C2 - 24699535
SN - 1932-6203
VL - 9
SP - e93057
JO - PLOS ONE
JF - PLOS ONE
IS - 4
ER -