CCR6-deficient mice suffer from increased brain edema after antibiotic therapy.

<p>(A) Infected mice with CCR6-deficiency developed more pronounced brain edema than infected wild type mice 48 h after infection, reflected in an increase in the estimated brain volume. (B) At the same time point, an increase of brain albumin content was noted in infected <i>Ccr6</i>^−/− mice, indicating blood-brain barrier disruption. These differences were only seen after but not before initiation of antibiotic therapy (24 h after infection). (C–G) Intracranial bleeding was similar in infected <i>Ccr6</i>^−/− and wild type mice. (*) p<0.05 compared with WT control animals. Number of animals: 24 h: <i>Ccr6</i>^−/− n = 12, WT n = 12; 48 h: <i>Ccr6</i>^−/− n = 12, WT n = 13.</p

CCL20 is expressed mainly during acute pneumococcal meningitis.

<p>(A) Increased CCL20 levels were found in mice brain homogenates during acute bacterial meningitis using ELISA. After initiation of antibiotic therapy (starting 24 h after infection), they decreased quickly to normal ((*) p<0.01 compared with uninfected controls). In uninfected control mice, (B, C) only a very subtle CCL20-positive staining was observed (white arrow). In contrast, in animals with pneumococcal meningitis, CCL20-positive staining was found in (D) epithel cells of the choroid plexus (black arrow) and (E) the subarachnoid inflammatory infiltrate (#). Number of animals: 6 h: n = 6, 24 h: n = 9, 30 h: n = 6, 48 h: n = 6, 72 h: n = 6, and 120 h: n = 7. Uninfected animals were used as controls (n = 11).</p

In patients with acute bacterial meningitis, (A) CCL20 cerebrospinal fluid (CSF) levels were significantly elevated compared with controls.

<p>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).</p

CCR6-deficient mice are more susceptible to pneumococcal meningitis.

<p>CCR6-deficient mice were more strongly affected from a clinical perspective by infection with <i>Streptococcus pneumoniae</i> than wild type controls. This was reflected (A) in increased clinical scores and (B) mortality. (C) CSF pleocytosis was lower in infected CCR6-deficient animals 24 h and 48 h after infection. (D) This was associated with higher brain bacterial titers at the time of initiation of antibiotic therapy (24 h after infection). (*) p<0.05 compared with infected wild type animals. Number of animals: 24 h: <i>Ccr6</i>^−/− n = 12, WT n = 12; 48 h: <i>Ccr6</i>^−/− n = 12, WT n = 13.</p

The pro-inflammatory effect of the CCL20/CCR6 axis seems independent of IL-17 production.

<p>IL17 was up-regulated in the CSF of (A) humans and (B) mice with pneumococcal meningitis. (C) However, antibody blockage of IL-17 in experimental pneumococcal meningitis did not lead to a reduction of inflammation in the CSF. P<0.05 as compared with uninfected controls. Number of animals: n = 5 mice per group.</p