Nevertheless, we MK2206 cannot rule out this possibility, since previous studies showed that during alveolar macrophage

infection, significantly more intracellular nonencapsulated S. pneumoniae were killed than the capsulated form [41]. In fact, we observed a reduction in the number of infected cells immediately after 3 h of association of S. pneumoniae with SCs followed at different times up to 24 h. Several aspects may be associated with this finding, including the ability of bacteria to escape from endocytic vesicles and then migrate to the extracellular environment [42], or die, either immediately after the adhesion or during internalization [39]. However, continued studies are necessary to better understand this mechanism in our model. Conclusions Our study Selleckchem BAY 11-7082 provided new insights into the molecular and cellular mechanisms by which S. pneumoniae can gain access to the CNS in the absence of bacteremia. The nasopharynx and maxillary sinuses are richly innervated by myelinated Combretastatin A4 mouse and non-myelinated sensory axons (and their associated Schwann cells) from the trigeminal nerve; thus, it can be predicted that any infection of SCs in these regions could provide a means of transport for S. pneumoniae

toward the brain along the peripheral nerves. Moreover, considering that S. pneumoniae is a common commensal in the nasopharynx of healthy adults and children, any surgical procedure in this region could result in a risk of contamination. Actually, pneumococcal meningitis may occur as a postoperative complication, due to invasion of multidrug-resistant S. pneumoniae strains from the nasopharynx after simultaneous osteotomy of the cranium and Mirabegron facial bone in intracraniofacial surgery [43]. Similarly, other nerves of

the head may also be important targets for infections, since pneumococcal meningitis is more likely in patients who received cochlear implantation through the surgical insertion technique in proximity to the auditory nerve in the inner ear (cochlea). Occasionally, in the presence of acute otitis media, it is possible that S. pneumoniae can reach the CNS via the auditory nerve [44]. In summary, our data offer novel evidence that SCs could be essential for pneumococcal cells to escape phagocytosis and killing by innate immune cells. On the other hand, the results also support the idea of SCs as immunocompetent cells of the PNS that can mediate an efficient immune response against pathogens via MR. Acknowledgments Financial support for this study was provided by the Vice-Presidency for Postgraduate Education of the Universidade Federal do Rio de Janeiro (CEPG/UFRJ), the Brazilian Council for Science and Technology (CNPq), and the Rio de Janeiro State Foundation for Research Support (FAPERJ). We are grateful to Dr. Tatiana C. Abreu Pinto for help with bacterial cultures and to Dr. Grasiella M. Ventura for her assistance in obtaining the confocal images. References 1.