Thus, it seems that PAFR is a direct receptor for meningococci and an indirect receptor for pneumococci. The inflammation induced by the presence of pneumococci leads to the release of cytokines by the Nigericin sodium salt endothelium, including inflammation mediators such as PAF, the ligand of PAFR. The PAFR signaling cascade leads to pro-inflammatory events and the activation of brain endothelial cells might facilitate transmigration of S. pneumoniae over cell layers, which would explain the PAFR involvement in IPD. PIgR is a well-known receptor for S. pneumoniae in epithelial cells. It has been implicated in the translocation of pneumococci over the epithelium through an intracellular pathway known as transcytosis. Absence of pIgR was reported in human brain endothelial cell line KC and in HUVEC, which led to the suggestion that pIgR could exclusively be an epithelial receptor for pneumococci. We detected pIgR in Detroit and not in A549 cells, as reported before, and also in HBMEC and HUVEC. The discrepancy concerning brain endothelial cells might be due to the use of different cell lines and different antihuman pIgR antibodies. We used HBMEC while Zhang et al used KC cell line, although both are immortalized human brain endothelial cell lines. No data on the absence of pIgR in HUVEC nor information on the provenance of the HUVEC was provided in the manuscript by Agarwal et al, whereas we used primary HUVEC isolated in house from different donors and clearly detected a pIgR signal by immunofluorescence and Western Blot analysis. For pIgR detection, Zhang et al. prepared a rabbit antiserum against human pIgR and a sheep antiserum against mouse pIgR. The R&D Systems antibodies used in our experiments detect the whole receptor, which has a NBD 556 molecular size of 100�C120 kDa, which corresponds to the molecular size of the band detected in our Western blot analysis. To assess the specificity of our anti-human pIgR antibody, we tested the antibody by immunofluorescent staining using Detroit and A549 cells respectively known as positive and negative pIgR-expressing cells. As expected from what was previously reported by Zhang et al, Detroit cells showed a relatively high expression of pIgR, while the receptor was not found in A549 cells. The anti-human pIgR antibody was also tested by Western blot analysis, and a pIgR specific band was present in Detroit cell lysate, while A549 did not show any receptor expression. Furthermore, we also included Beas2b cells as additional negative control. Based on the immunofluorescent and Western blot results using control cells such as Detroit, A549 and Beas2b, we concluded that we indeed detected expression of pIgR in HBMEC and HUVEC.