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Ion of pIgR and nuclei in lungs of mock-treated and infected mice. Total magnification 630X. Data S1 Three-dimensional visualization of S. pneumoniae and pIgR inside the subarachnoid space of infected mice detected by confocal microscopy. Acknowledgments A part of the operate was performed in the UMCG Microscopy and Imaging Center. We thank Henk Moorlag from the UMCG Endothelial Cell Facility for delivering HUVEC and for cryostat cutting of tissue sections. We also thank Dr. Henrik Gradstedt for giving the antipneumococcal antiserum and Prof. dr. Jan Maarten van Dijl for the comments on the manuscript. Author Contributions Conceived and made the experiments: FI GM JB. Performed the experiments: FI. Analyzed the data: FI GM JB. Contributed reagents/ materials/analysis tools: GM JB. Wrote the paper: FI GM JB. ten Pneumococci Interact with Endothelial pIgR References 1. Mook-Kanamori BB, Geldhoff M, van der Poll T, van de Beek D Pathogenesis and pathophysiology of pneumococcal meningitis. Clin Microbiol Rev 24: 55791. two. Bogaert D, De Groot R, Hermans PW Streptococcus pneumoniae colonisation: the essential to pneumococcal illness. Lancet Infect Dis 4: 14454. three. Woehrl B, Klein M, Grandgirard D, Koedel U, Leib S Bacterial meningitis: present therapy and possible future treatment selections. Specialist Rev Anti Infect Ther 9: 105365. 4. Koedel U, Scheld WM, Pfister HW Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis 2: 72136. 5. Ring A, Weiser JN, Tuomanen EI Pneumococcal trafficking across the 23115181 blood-brain barrier. Molecular evaluation of a novel bidirectional pathway. J Clin Invest 102: 34760. six. Radin JN, Orihuela CJ, Murti G, Guglielmo C, Murray PJ, et al. BetaArrestin 1 participates in platelet-activating element receptor-mediated endocytosis of Streptococcus pneumoniae. Infect Immun 73: 782735. 7. Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating element. Nature 377: 4358. eight. Iovino F, Brouwer MC, van de Beek D, Molema G, Bijlsma JJ Signaling or binding: the function on the 478-01-3 web platelet activating issue receptor in invasive pneumococcal disease. Cell Microbiol 15: 87081 9. Zhang JR, Mostov KE, Lamm ME, Nanno M, Shimida S, et al. The polymeric H 4065 price immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102: 82737. ten. Luo R, Mann B, Lewis WS, Rowe A, Heath R, et al. Remedy structure of choline binding protein A, the important adhesin of Streptococcus pneumoniae. EMBO J 24: 3443. 11. Ikonen E, Parton RG, Hunziker W, Simons K, Dotti CG Transcytosis with the polymeric immunoglobulin receptor in cultured hippocampal neurons. Curr Biol three: 63544. 12. de Hoop M, von Poser C, Lange C, Ikonen E, Hunziker W, et al. Intracellular routing of wild-type and mutated polymeric immunoglobulin receptor in hippocampal neurons in culture. J Cell Biol 130: 144759. 13. Hemar A, Olivo JC, Williamson E, Saffrich R, Dotti CG Dendroaxonal transcytosis of transferrin in cultured hippocampal and sympathetic neurons. J Neurosci 17: 902634. 14. Stins MF, Badger J, Sik Kim K Bacterial invasion and transcytosis in transfected human brain microvascular endothelial cells. Microb Pathog 30: 19 28. 15. Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, et al. In vitro cultivation of human tumors: establishment of cell lines derived from a series of strong tumors. J Natl Cancer Inst 51: 141723. 16. Romero-Steiner S, Caba.Ion of pIgR and nuclei in lungs of mock-treated and infected mice. Total magnification 630X. Data S1 Three-dimensional visualization of S. pneumoniae and pIgR in the subarachnoid space of infected mice detected by confocal microscopy. Acknowledgments Part of the operate was performed in the UMCG Microscopy and Imaging Center. We thank Henk Moorlag from the UMCG Endothelial Cell Facility for offering HUVEC and for cryostat cutting of tissue sections. We also thank Dr. Henrik Gradstedt for providing the antipneumococcal antiserum and Prof. dr. Jan Maarten van Dijl for the comments on the manuscript. Author Contributions Conceived and created the experiments: FI GM JB. Performed the experiments: FI. Analyzed the information: FI GM JB. Contributed reagents/ materials/analysis tools: GM JB. Wrote the paper: FI GM JB. 10 Pneumococci Interact with Endothelial pIgR References 1. Mook-Kanamori BB, Geldhoff M, van der Poll T, van de Beek D Pathogenesis and pathophysiology of pneumococcal meningitis. Clin Microbiol Rev 24: 55791. 2. Bogaert D, De Groot R, Hermans PW Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis four: 14454. 3. Woehrl B, Klein M, Grandgirard D, Koedel U, Leib S Bacterial meningitis: existing therapy and attainable future remedy alternatives. Specialist Rev Anti Infect Ther 9: 105365. four. Koedel U, Scheld WM, Pfister HW Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis two: 72136. 5. Ring A, Weiser JN, Tuomanen EI Pneumococcal trafficking across the 23115181 blood-brain barrier. Molecular analysis of a novel bidirectional pathway. J Clin Invest 102: 34760. six. Radin JN, Orihuela CJ, Murti G, Guglielmo C, Murray PJ, et al. BetaArrestin 1 participates in platelet-activating aspect receptor-mediated endocytosis of Streptococcus pneumoniae. Infect Immun 73: 782735. 7. Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating issue. Nature 377: 4358. eight. Iovino F, Brouwer MC, van de Beek D, Molema G, Bijlsma JJ Signaling or binding: the role of the platelet activating issue receptor in invasive pneumococcal disease. Cell Microbiol 15: 87081 9. Zhang JR, Mostov KE, Lamm ME, Nanno M, Shimida S, et al. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102: 82737. 10. Luo R, Mann B, Lewis WS, Rowe A, Heath R, et al. Option structure of choline binding protein A, the significant adhesin of Streptococcus pneumoniae. EMBO J 24: 3443. 11. Ikonen E, Parton RG, Hunziker W, Simons K, Dotti CG Transcytosis in the polymeric immunoglobulin receptor in cultured hippocampal neurons. Curr Biol 3: 63544. 12. de Hoop M, von Poser C, Lange C, Ikonen E, Hunziker W, et al. Intracellular routing of wild-type and mutated polymeric immunoglobulin receptor in hippocampal neurons in culture. J Cell Biol 130: 144759. 13. Hemar A, Olivo JC, Williamson E, Saffrich R, Dotti CG Dendroaxonal transcytosis of transferrin in cultured hippocampal and sympathetic neurons. J Neurosci 17: 902634. 14. Stins MF, Badger J, Sik Kim K Bacterial invasion and transcytosis in transfected human brain microvascular endothelial cells. Microb Pathog 30: 19 28. 15. Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, et al. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 51: 141723. 16. Romero-Steiner S, Caba.

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