Acute brain injury triggers MyD88-dependent, TLR2/4-independent inflammatory responses.

Endogenous molecules released from disrupted cells and extracellular matrix degradation products activate Toll-like receptors (TLRs) and, thus, might contribute to immune activation after tissue injury. Here, we show that aseptic, cold-induced cortical injury triggered an acute immune response that involves increased production of multiple cytokines/chemokines accompanied by neutrophil recruitment to the lesion site. We observed selective reductions in injury-induced cytokine/chemokine expression as well as in neutrophil accumulation in mice lacking the common TLR signaling adaptor MyD88 compared with wild-type mice.

Borrelia garinii induces CXCL13 production in human monocytes through Toll-like receptor 2.

Recent studies have suggested an important role for the B-cell-attracting chemokine CXCL13 in the B-cell-dominated cerebrospinal fluid (CSF) infiltrate in patients with neuroborreliosis (NB). High levels of CXCL13 were present in the CSF of NB patients. It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well.

MyD88-dependent immune response contributes to hearing loss in experimental pneumococcal meningitis.

Hearing loss is one of the most common sequelae in survivors of pneumococcal meningitis, affecting up to 26% of them. Here, we established the first mouse model of meningitis-associated hearing loss and investigated the role played by the Toll-like receptor-associated adapter molecule MyD88. C57BL/6 mice were infected intracisternally by Streptococcus pneumoniae.

Differential regulation of blood-brain barrier permeability in brain trauma and pneumococcal meningitis-role of Src kinases.

Increased vascular permeability causing vasogenic brain edema is characteristic for many acute neurological diseases such as stroke, brain trauma, and meningitis. Src family kinases, especially c-Src, play an important role in regulating blood-brain barrier permeability in response to VEGF, but also mediate leukocyte function and cytokine signalling. Here we demonstrate that pharmacological inhibition of Src or c-Src deficiency does not influence cerebrospinal fluid (CSF) pleocytosis, brain edema formation, and bacterial outgrowth during experimental pneumococcal meningitis despite the increased cerebral expression of inflammatory chemokines, such as IL-6, CCL-9, CXCL-1, CXCL-2 and G-CSF as determined by protein array analysis.

Protein expression pattern in experimental pneumococcal meningitis.

In this study, we investigated cytokine expression during experimental pneumococcal meningitis. Mice were intracisternally infected with Streptococcus pneumoniae and treated with ceftriaxone starting at 24 h after infection. At different time points before and after antibiotic therapy, the cytokine expression pattern was determined in mouse brains using protein arrays.

Urokinase-type plasminogen activator receptor regulates leukocyte recruitment during experimental pneumococcal meningitis.

Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) have been suggested to play an important role in inflammatory diseases. Increased levels of tPA, uPA, uPA receptor (uPAR), and their inhibitor, plasminogen activator inhibitor (PAI)-1, have been found in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. Here, we show that expression of tPA, uPA, uPAR, PAI-1, and PAI-2 is up-regulated during experimental pneumococcal meningitis.