Staphylococcus aureus is inherently resistant to cationic antimicrobial peptides because of alanylation of cell envelope teichoic acids. To test the effect of alanylated teichoic acids on virulence and host defense mediated by Toll-like receptor 2 (TLR2), wild-type (wt) S. aureus ATCC35556 (S.a.113) and its isogenic mutant expressing unalanylated teichoic acids (dlt(-)) were compared in a tissue cage infection model that used C57BL/6 wt and TLR2-deficient mice. The minimum infective doses (MID) to establish persistent infection with S.a.113 were 10(3) and 10(2) colony-forming units (cfu) in wt and TLR2(-/-) mice, respectively. The corresponding MID for dlt(-) were 5x105 and 10(3) cfu in wt and TLR2(-/-) mice, respectively. Both mouse strains showed bacterial-load-dependent inflammation with elevations in tumor necrosis factor, macrophage inflammatory protein 2, and leukocytes, with increasing proportions of dead cells. These findings indicate that alanylated teichoic acids contribute to virulence of S. aureus, and TLR2 mediates host defense, which partly targets alanylated teichoic acids.

Type I IFNs represent a major antimicrobial defense mechanism due to their property of enhancing immune responses by priming both innate and adaptive immune cells. Plasmacytoid dendritic cells (pDC) are the major source of type I IFN in the human body and represent innate immune cells involved in first-line defense against invading pathogens. Although pDC activation has been extensively studied upon stimulation with synthetic TLR ligands, viruses, and intracellular bacteria, there is only scarce information on extracellular bacteria. In this study we show that the triggering of human pDC-derived IFN-α secretion by Staphylococcus aureus is independent of TLR2 and specific for coagulase-positive staphylococci. Specificity of the pDC response to S. aureus is independent of the bacterial virulence factors protein A and α-toxin but is mediated by Ag-specific IgG and CD32. S. aureus-induced pDC activation can be blocked by inhibitory DNA oligonucleotides and chloroquine, suggesting that engagement of TLR7/9 by bacterial nucleic acids after CD32-mediated uptake of these compounds may play a central role in this process. Altogether, we propose that in marked contrast to nonselective TLR2-dependent activation of most innate immune cells, pDC activation by S. aureus represents an Ag-specific memory response since it requires the presence of class-switched immunoglobulins.

Peptidoglycans (PGN) from bacterial cell walls may modify the course of an infection with bacterial pathogens. The present study explored the effect of PGN on cytosolic Ca²⁺ activity, cytokine production and phagocytosis of mouse dendritic cells (DCs), essential cells in the initiation and direction of antigen-specific T cell responses. Exposure of DCs to PGN was followed by a rapid increase in cytosolic Ca²⁺ activity ([Ca²⁺]_i), which was due to Ca²⁺ release from intracellular stores and influx of extracellular Ca²⁺ across the cell membrane. In DCs isolated from Toll-like receptor 2 (TLR2) deficient mice the effect of PGN on [Ca²⁺]_i was dramatically impaired. The PGN-induced increase of [Ca²⁺]_i was dependent on voltage-gated K⁺ (Kv) channel activity. PGN-induced increase of [Ca²⁺]_i was significantly blunted by margatoxin (MgTx) and perhexiline maleate (PM), inhibitors of Kv1.3 and Kv1.5, respectively. PGN further stimulated the release of tumour necrosis factor α (TNFα), interleukin-12 (IL-12) and interleukin-10 (IL-10), an effect significantly blunted by PM and the specific blocker of store-operated Ca²⁺ channels SKF-96365. Moreover, phagocytic capacity was dramatically increased in PGN-stimulated DCs in the presence of either Kv channel inhibitors or SKF-96365. The observations disclose Ca²⁺ and Kv channel-dependent cytokine production and phagocytosis in PGN-stimulated DCs.

• Radiological (CT and MR) features are of crucial importance for cochlear implantation • Imaging can identify two types of incomplete cochlear partition and atypical cases • Detailed pre-operative radiological assessment can help predict complications and outcome • A more comprehensive radiological classification of these anomalies is proposed.

Vestibulocochlear nerve deficiency can be strongly suspected in certain inner ear malformations • Bony cochlear aplasia and cochlear nerve aplasia are strongly correlated • In semicircular canal aplasia, hypoplasia of the vestibular nerve can be found • Before cochlear implantation, the type of any IEM should be fully understood.