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

Klein M, Brouwer MC, Angele B, Geldhoff M, Marquez G, Varona R, Häcker G, Schmetzer H, Häcker H, Hammerschmidt S, van der Ende A, Pfister HW, van de Beek D, Koedel U - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.

ABSTRACT
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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In patients with acute bacterial meningitis, (A) CCL20 cerebrospinal fluid (CSF) levels were significantly elevated compared with controls.CCL20 CSF levels of patients with pneumococcal meningitis correlated to (B) CSF white blood cell (WBC) counts, (C) CSF blood glucose ratio, and (D) CSF protein levels (see text for details).
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pone-0093057-g001: In patients with acute bacterial meningitis, (A) CCL20 cerebrospinal fluid (CSF) levels were significantly elevated compared with controls.CCL20 CSF levels of patients with pneumococcal meningitis correlated to (B) CSF white blood cell (WBC) counts, (C) CSF blood glucose ratio, and (D) CSF protein levels (see text for details).

Mentions: To evaluate CCL20 during acute pneumococcal meningitis in humans we used patients from a nationwide prospective cohort study, performed from 2006–2010. In this study, 526 patients (73%) suffered from S. pneumoniae meningitis, Neisseria meningitidis was found in 90 (13%) episodes, Listeria monocytogenes in 35 (5%) episodes, and others in 68 (9%) episodes [28]. CSF from diagnostic lumbar puncture was available for 203 of 526 episodes of pneumococcal meningitis (39%). We also selected 19 patients with normal CSF who underwent CSF examination to exclude subarachnoid hemorrhage and 24 patients with viral meningitis as controls. In patients with pneumococcal meningitis, the median CSF CCL20 concentration was 6.9 ng/ml (interquartile range [IQR] 1.20–17.1). 96% of samples were above the lower limit of detection (33 pg/ml). CCL20 levels in negative controls and patients with viral meningitis were significantly lower than those of bacterial meningitis patients (Figure 1A). CCL20 CSF levels were correlated to CSF white blood cell (WBC) counts (Figure 1B, Coefficient: 0.175, p = 0.019), CSF blood-glucose ratio (Figure 1C, Coefficient: −0.388, p<0.001), and CSF protein levels (Figure 1D, Coefficient: 0.576, p<0.001).


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

Klein M, Brouwer MC, Angele B, Geldhoff M, Marquez G, Varona R, Häcker G, Schmetzer H, Häcker H, Hammerschmidt S, van der Ende A, Pfister HW, van de Beek D, Koedel U - PLoS ONE (2014)

In patients with acute bacterial meningitis, (A) CCL20 cerebrospinal fluid (CSF) levels were significantly elevated compared with controls.CCL20 CSF levels of patients with pneumococcal meningitis correlated to (B) CSF white blood cell (WBC) counts, (C) CSF blood glucose ratio, and (D) CSF protein levels (see text for details).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974727&req=5

pone-0093057-g001: In patients with acute bacterial meningitis, (A) CCL20 cerebrospinal fluid (CSF) levels were significantly elevated compared with controls.CCL20 CSF levels of patients with pneumococcal meningitis correlated to (B) CSF white blood cell (WBC) counts, (C) CSF blood glucose ratio, and (D) CSF protein levels (see text for details).
Mentions: To evaluate CCL20 during acute pneumococcal meningitis in humans we used patients from a nationwide prospective cohort study, performed from 2006–2010. In this study, 526 patients (73%) suffered from S. pneumoniae meningitis, Neisseria meningitidis was found in 90 (13%) episodes, Listeria monocytogenes in 35 (5%) episodes, and others in 68 (9%) episodes [28]. CSF from diagnostic lumbar puncture was available for 203 of 526 episodes of pneumococcal meningitis (39%). We also selected 19 patients with normal CSF who underwent CSF examination to exclude subarachnoid hemorrhage and 24 patients with viral meningitis as controls. In patients with pneumococcal meningitis, the median CSF CCL20 concentration was 6.9 ng/ml (interquartile range [IQR] 1.20–17.1). 96% of samples were above the lower limit of detection (33 pg/ml). CCL20 levels in negative controls and patients with viral meningitis were significantly lower than those of bacterial meningitis patients (Figure 1A). CCL20 CSF levels were correlated to CSF white blood cell (WBC) counts (Figure 1B, Coefficient: 0.175, p = 0.019), CSF blood-glucose ratio (Figure 1C, Coefficient: −0.388, p<0.001), and CSF protein levels (Figure 1D, Coefficient: 0.576, p<0.001).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus