{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:08:45Z","timestamp":1789758525341,"version":"4.0.1"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Research Training Program Australia"},{"DOI":"10.13039\/501100014673","name":"Menzies Health Institute Queensland","doi-asserted-by":"publisher","award":["Capacity grant"],"award-info":[{"award-number":["Capacity grant"]}],"id":[{"id":"10.13039\/501100014673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014673","name":"Menzies Health Institute Queensland","doi-asserted-by":"publisher","award":["Capacity grant"],"award-info":[{"award-number":["Capacity grant"]}],"id":[{"id":"10.13039\/501100014673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014673","name":"Menzies Health Institute Queensland","doi-asserted-by":"publisher","award":["Capacity grant"],"award-info":[{"award-number":["Capacity grant"]}],"id":[{"id":"10.13039\/501100014673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001791","name":"Griffith University","doi-asserted-by":"publisher","award":["New Research Grant"],"award-info":[{"award-number":["New Research Grant"]}],"id":[{"id":"10.13039\/501100001791","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021518","name":"Perry Cross Spinal Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021518","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008763","name":"Clem Jones Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008763","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Staphylococcus aureus<\/jats:italic>infections of the central nervous system are serious and can be fatal.<jats:italic>S. aureus<\/jats:italic>is commonly present in the nasal cavity, and after injury to the nasal epithelium it can rapidly invade the brain via the olfactory nerve. The trigeminal nerve constitutes another potential route of brain infection. The glia of these nerves, olfactory ensheathing cells (OECs) and trigeminal nerve Schwann cells (TgSCs), as well as astrocytes populating the glia limitans layer, can phagocytose bacteria. Whilst some glial responses to<jats:italic>S. aureus<\/jats:italic>have been studied, the specific responses of different glial types are unknown. Here, we compared how primary mouse OECs, TgSCs, astrocytes and microglia responded to<jats:italic>S. aureus<\/jats:italic>. All glial types internalized the bacteria within phagolysosomes, and<jats:italic>S. aureus<\/jats:italic>-conjugated BioParticles could be tracked with subtle but significant differences in time-course of phagocytosis between glial types. Live bacteria could be isolated from all glia after 24 h in culture, and microglia, OECs and TgSCs exhibited better protection against intracellular<jats:italic>S. aureus<\/jats:italic>survival than astrocytes. All glial types responded to the bacteria by cytokine secretion. Overall, OECs secreted the lowest level of cytokines, suggesting that these cells, despite showing strong capacity for phagocytosis, have immunomodulatory functions that can be relevant for neural repair.<\/jats:p>","DOI":"10.1038\/s41598-021-90252-0","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T10:02:50Z","timestamp":1621591370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Antimicrobial responses of peripheral and central nervous system glia against Staphylococcus aureus"],"prefix":"10.1038","volume":"11","author":[{"given":"Indra N.","family":"Choudhury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Chacko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Delbaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souptik","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"St John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Huygens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny A. K.","family":"Ekberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"90252_CR1","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1007\/s12035-012-8320-7","volume":"46","author":"G De Chiara","year":"2012","unstructured":"De Chiara, G. et al. Infectious agents and neurodegeneration. Mol. Neurobiol. 46, 614\u2013638 (2012).","journal-title":"Mol. Neurobiol."},{"key":"90252_CR2","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1128\/CMR.00118-13","volume":"27","author":"SJ Dando","year":"2014","unstructured":"Dando, S. J. et al. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clin. Microbiol. Rev. 27, 691\u2013726. https:\/\/doi.org\/10.1128\/CMR.00118-13 (2014).","journal-title":"Clin. Microbiol. Rev."},{"key":"90252_CR3","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/j.1749-6632.1985.tb20802.x","volume":"457","author":"PP Graziadei","year":"1985","unstructured":"Graziadei, P. P. & Monti Graziadei, G. A. Neurogenesis and plasticity of the olfactory sensory neurons. Ann. N. Y. Acad. Sci. 457, 127\u2013142 (1985).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"90252_CR4","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/j.1460-9568.1991.tb00081.x","volume":"3","author":"A Mackay-Sim","year":"1991","unstructured":"Mackay-Sim, A. & Kittel, P. W. On the life span of olfactory receptor neurons. Eur. J. Neurosci. 3, 209\u2013215. https:\/\/doi.org\/10.1111\/j.1460-9568.1991.tb00081.x (1991).","journal-title":"Eur. J. Neurosci."},{"key":"90252_CR5","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/0166-2236(90)90017-5","volume":"13","author":"AI Farbman","year":"1990","unstructured":"Farbman, A. I. Olfactory neurogenesis: genetic or environmental controls?. Trends Neurosci. 13, 362\u2013365. https:\/\/doi.org\/10.1016\/0166-2236(90)90017-5 (1990).","journal-title":"Trends Neurosci."},{"key":"90252_CR6","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/cne.10143","volume":"444","author":"ML Schaefer","year":"2002","unstructured":"Schaefer, M. L., Bottger, B., Silver, W. L. & Finger, T. E. Trigeminal collaterals in the nasal epithelium and olfactory bulb: a potential route for direct modulation of olfactory information by trigeminal stimuli. J. Comp. Neurol. 444, 221\u2013226. https:\/\/doi.org\/10.1002\/cne.10143 (2002).","journal-title":"J. Comp. Neurol."},{"key":"90252_CR7","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1172\/JCI128865","volume":"130","author":"SP Jochems","year":"2019","unstructured":"Jochems, S. P. et al. Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization. J. Clin. Invest. 130, 4523\u20134538. https:\/\/doi.org\/10.1172\/JCI128865 (2019).","journal-title":"J. Clin. Invest."},{"key":"90252_CR8","doi-asserted-by":"publisher","first-page":"5205","DOI":"10.1038\/ncomms6205","volume":"5","author":"L Tacchi","year":"2014","unstructured":"Tacchi, L. et al. Nasal immunity is an ancient arm of the mucosal immune system of vertebrates. Nat. Commun. 5, 5205. https:\/\/doi.org\/10.1038\/ncomms6205 (2014).","journal-title":"Nat. Commun."},{"key":"90252_CR9","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/glia.22450","volume":"61","author":"Z Su","year":"2013","unstructured":"Su, Z. et al. Olfactory ensheathing cells: the primary innate immunocytes in the olfactory pathway to engulf apoptotic olfactory nerve debris. Glia 61, 490\u2013503. https:\/\/doi.org\/10.1002\/glia.22450 (2013).","journal-title":"Glia"},{"key":"90252_CR10","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/glia.20149","volume":"49","author":"K Wewetzer","year":"2005","unstructured":"Wewetzer, K., Kern, N., Ebel, C., Radtke, C. & Brandes, G. Phagocytosis of O4+ axonal fragments in vitro by p75- neonatal rat olfactory ensheathing cells. Glia 49, 577\u2013587. https:\/\/doi.org\/10.1002\/glia.20149 (2005).","journal-title":"Glia"},{"key":"90252_CR11","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1002\/cne.23694","volume":"523","author":"L Nazareth","year":"2015","unstructured":"Nazareth, L. et al. Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system. J. Comp. Neurol. 523, 479\u2013494. https:\/\/doi.org\/10.1002\/cne.23694 (2015).","journal-title":"J. Comp. Neurol."},{"key":"90252_CR12","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1002\/glia.20899","volume":"57","author":"JA Harris","year":"2009","unstructured":"Harris, J. A., West, A. K. & Chuah, M. I. Olfactory ensheathing cells: nitric oxide production and innate immunity. Glia 57, 1848\u20131857. https:\/\/doi.org\/10.1002\/glia.20899 (2009).","journal-title":"Glia"},{"key":"90252_CR13","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/1742-2094-9-109","volume":"9","author":"RP Herbert","year":"2012","unstructured":"Herbert, R. P. et al. Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway. J. Neuroinflam. 9, 109. https:\/\/doi.org\/10.1186\/1742-2094-9-109 (2012).","journal-title":"J. Neuroinflam."},{"key":"90252_CR14","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/glia.20512","volume":"55","author":"AJ Vincent","year":"2007","unstructured":"Vincent, A. J., Choi-Lundberg, D. L., Harris, J. A., West, A. K. & Chuah, M. I. Bacteria and PAMPs activate nuclear factor kappaB and Gro production in a subset of olfactory ensheathing cells and astrocytes but not in Schwann cells. Glia 55, 905\u2013916. https:\/\/doi.org\/10.1002\/glia.20512 (2007).","journal-title":"Glia"},{"key":"90252_CR15","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1007\/s00018-008-8184-1","volume":"65","author":"JY Leung","year":"2008","unstructured":"Leung, J. Y. et al. Olfactory ensheathing cells are attracted to, and can endocytose, bacteria. Cell Mol. Life Sci. 65, 2732\u20132739. https:\/\/doi.org\/10.1007\/s00018-008-8184-1 (2008).","journal-title":"Cell Mol. Life Sci."},{"key":"90252_CR16","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.neulet.2013.01.052","volume":"539","author":"P Panni","year":"2013","unstructured":"Panni, P. et al. Phagocytosis of bacteria by olfactory ensheathing cells and Schwann cells. Neurosci. Lett. 539, 65\u201370. https:\/\/doi.org\/10.1016\/j.neulet.2013.01.052 (2013).","journal-title":"Neurosci. Lett."},{"key":"90252_CR17","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1002\/cne.24618","volume":"527","author":"L Nazareth","year":"2019","unstructured":"Nazareth, L. et al. Novel insights into the glia limitans of the olfactory nervous system. J. Comp. Neurol. 527, 1228\u20131244. https:\/\/doi.org\/10.1002\/cne.24618 (2019).","journal-title":"J. Comp. Neurol."},{"key":"90252_CR18","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3389\/fnmol.2019.00057","volume":"12","author":"S Geyer","year":"2019","unstructured":"Geyer, S., Jacobs, M. & Hsu, N. J. Immunity against bacterial infection of the central nervous system: an astrocyte perspective. Front Mol. Neurosci. 12, 57. https:\/\/doi.org\/10.3389\/fnmol.2019.00057 (2019).","journal-title":"Front Mol. Neurosci."},{"key":"90252_CR19","doi-asserted-by":"publisher","first-page":"350","DOI":"10.4062\/biomolther.2017.133","volume":"26","author":"Y-J Jung","year":"2018","unstructured":"Jung, Y.-J. & Chung, W.-S. Phagocytic roles of glial cells in healthy and diseased brains. Biomol. Ther. (Seoul) 26, 350\u2013357. https:\/\/doi.org\/10.4062\/biomolther.2017.133 (2018).","journal-title":"Biomol. Ther. (Seoul)"},{"key":"90252_CR20","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/1742-2094-9-115","volume":"9","author":"B Stansley","year":"2012","unstructured":"Stansley, B., Post, J. & Hensley, K. A comparative review of cell culture systems for the study of microglial biology in Alzheimer\u2019s disease. J. Neuroinflam. 9, 115. https:\/\/doi.org\/10.1186\/1742-2094-9-115 (2012).","journal-title":"J. Neuroinflam."},{"key":"90252_CR21","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/S0165-5728(02)00216-3","volume":"130","author":"T Kielian","year":"2002","unstructured":"Kielian, T., Mayes, P. & Kielian, M. Characterization of microglial responses to Staphylococcus aureus: effects on cytokine, costimulatory molecule, and Toll-like receptor expression. J. Neuroimmunol. 130, 86\u201399. https:\/\/doi.org\/10.1016\/S0165-5728(02)00216-3 (2002).","journal-title":"J. Neuroimmunol."},{"key":"90252_CR22","doi-asserted-by":"publisher","first-page":"e02209","DOI":"10.1128\/JVI.02209-18","volume":"93","author":"JR Doll","year":"2019","unstructured":"Doll, J. R., Thompson, R. L. & Sawtell, N. M. Infectious herpes simplex virus in the brain stem is correlated with reactivation in the trigeminal ganglia. J. Virol. 93, e02209-02218 (2019).","journal-title":"J. Virol."},{"key":"90252_CR23","first-page":"42","volume":"28","author":"MC Brouwer","year":"2020","unstructured":"Brouwer, M. C., Ascione, T. & Pagliano, P. Neurologic aspects of covid-19: a concise review. Infez. Med. 28, 42\u201345 (2020).","journal-title":"Infez. Med."},{"key":"90252_CR24","doi-asserted-by":"publisher","first-page":"e0008017","DOI":"10.1371\/journal.pntd.0008017","volume":"14","author":"H Walkden","year":"2020","unstructured":"Walkden, H. et al. Burkholderia pseudomallei invades the olfactory nerve and bulb after epithelial injury in mice and causes the formation of multinucleated giant glial cells in vitro. PLoS Negl. Trop. Dis. 14, e0008017. https:\/\/doi.org\/10.1371\/journal.pntd.0008017 (2020).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"90252_CR25","doi-asserted-by":"publisher","first-page":"e10598","DOI":"10.1371\/journal.pone.0010598","volume":"5","author":"DN Frank","year":"2010","unstructured":"Frank, D. N. et al. The human nasal microbiota and Staphylococcus aureus carriage. PLoS ONE 5, e10598\u2013e10598. https:\/\/doi.org\/10.1371\/journal.pone.0010598 (2010).","journal-title":"PLoS ONE"},{"key":"90252_CR26","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1001\/archinte.153.16.1902","volume":"153","author":"AG Jensen","year":"1993","unstructured":"Jensen, A. G., Espersen, F., Skinhoj, P., Rosdahl, V. T. & Frimodt-Moller, N. Staphylococcus aureus meningitis. A review of 104 nationwide, consecutive cases. Arch. Intern. Med. 153, 1902\u20131908. https:\/\/doi.org\/10.1001\/archinte.153.16.1902 (1993).","journal-title":"Arch. Intern. Med."},{"key":"90252_CR27","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/1471-2334-6-49","volume":"6","author":"M Pedersen","year":"2006","unstructured":"Pedersen, M., Benfield, T. L., Skinhoej, P. & Jensen, A. G. Haematogenous Staphylococcus aureus meningitis. A 10-year nationwide study of 96 consecutive cases. BMC Infect. Dis. 6, 49. https:\/\/doi.org\/10.1186\/1471-2334-6-49 (2006).","journal-title":"BMC Infect. Dis."},{"key":"90252_CR28","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1086\/515541","volume":"25","author":"GE Mathisen","year":"1997","unstructured":"Mathisen, G. E. & Johnson, J. P. Brain abscess. Clin. Infect. Dis. 25, 763\u2013779. https:\/\/doi.org\/10.1086\/515541 (1997).","journal-title":"Clin. Infect. Dis."},{"key":"90252_CR29","first-page":"403","volume":"43","author":"GC Townsend","year":"1998","unstructured":"Townsend, G. C. & Scheld, W. M. Infections of the central nervous system. Adv. Intern. Med. 43, 403\u2013447 (1998).","journal-title":"Adv. Intern. Med."},{"key":"90252_CR30","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s00109-010-0630-5","volume":"88","author":"TR Sheen","year":"2010","unstructured":"Sheen, T. R. et al. Penetration of the blood-brain barrier by Staphylococcus aureus: contribution of membrane-anchored lipoteichoic acid. J. Mol. Med. (Berl.) 88, 633\u2013639. https:\/\/doi.org\/10.1007\/s00109-010-0630-5 (2010).","journal-title":"J. Mol. Med. (Berl.)"},{"key":"90252_CR31","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s12866-014-0211-9","volume":"14","author":"H Macedo-Ramos","year":"2014","unstructured":"Macedo-Ramos, H. et al. Evidence of involvement of the mannose receptor in the internalization of Streptococcus pneumoniae by Schwann cells. BMC Microbiol. 14, 211. https:\/\/doi.org\/10.1186\/s12866-014-0211-9 (2014).","journal-title":"BMC Microbiol."},{"key":"90252_CR32","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00955-19","author":"A Delbaz","year":"2020","unstructured":"Delbaz, A. et al. Neisseria meningitidis induces pathology-associated cellular and molecular changes in trigeminal Schwann cells. Infect. Immun. https:\/\/doi.org\/10.1128\/IAI.00955-19 (2020).","journal-title":"Infect. Immun."},{"key":"90252_CR33","doi-asserted-by":"publisher","first-page":"549","DOI":"10.4161\/auto.28448","volume":"10","author":"DJ Klionsky","year":"2014","unstructured":"Klionsky, D. J., Eskelinen, E. L. & Deretic, V. Autophagosomes, phagosomes, autolysosomes, phagolysosomes, autophagolysosomes wait\u2026 I\u2019m confused. Autophagy 10, 549\u2013551. https:\/\/doi.org\/10.4161\/auto.28448 (2014).","journal-title":"Autophagy"},{"key":"90252_CR34","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1007\/s12035-013-8620-6","volume":"49","author":"R Fu","year":"2014","unstructured":"Fu, R., Shen, Q., Xu, P., Luo, J. J. & Tang, Y. Phagocytosis of microglia in the central nervous system diseases. Mol. Neurobiol. 49, 1422\u20131434. https:\/\/doi.org\/10.1007\/s12035-013-8620-6 (2014).","journal-title":"Mol. Neurobiol."},{"key":"90252_CR35","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.bcp.2016.07.011","volume":"116","author":"TS Kapellos","year":"2016","unstructured":"Kapellos, T. S. et al. A novel real time imaging platform to quantify macrophage phagocytosis. Biochem. Pharmacol. 116, 107\u2013119. https:\/\/doi.org\/10.1016\/j.bcp.2016.07.011 (2016).","journal-title":"Biochem. Pharmacol."},{"key":"90252_CR36","doi-asserted-by":"publisher","first-page":"e0196153","DOI":"10.1371\/journal.pone.0196153","volume":"13","author":"NM Wakida","year":"2018","unstructured":"Wakida, N. M. et al. Phagocytic response of astrocytes to damaged neighboring cells. PLoS ONE 13, e0196153. https:\/\/doi.org\/10.1371\/journal.pone.0196153 (2018).","journal-title":"PLoS ONE"},{"key":"90252_CR37","doi-asserted-by":"crossref","unstructured":"Byun, Y. G. & Chung, W.-S. in Astrocytes: Methods and Protocols (ed Barbara Di Benedetto) 155\u2013168 (Springer New York, 2019).","DOI":"10.1007\/978-1-4939-9068-9_11"},{"key":"90252_CR38","doi-asserted-by":"publisher","first-page":"e42660","DOI":"10.1371\/journal.pone.0042660","volume":"7","author":"K Alkuwaity","year":"2012","unstructured":"Alkuwaity, K., Taylor, A., Heckels, J. E., Doran, K. S. & Christodoulides, M. Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro. PLoS ONE 7, e42660\u2013e42660. https:\/\/doi.org\/10.1371\/journal.pone.0042660 (2012).","journal-title":"PLoS ONE"},{"key":"90252_CR39","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1046\/j.1471-4159.2003.02202.x","volume":"88","author":"N Esen","year":"2004","unstructured":"Esen, N., Tanga, F. Y., DeLeo, J. A. & Kielian, T. Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus. J. Neurochem. 88, 746\u2013758. https:\/\/doi.org\/10.1046\/j.1471-4159.2003.02202.x (2004).","journal-title":"J. Neurochem."},{"key":"90252_CR40","first-page":"341","volume":"6","author":"GZ Feuerstein","year":"1994","unstructured":"Feuerstein, G. Z., Liu, T. & Barone, F. C. Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha. Cerebrovasc. Brain Metab. Rev. 6, 341\u2013360 (1994).","journal-title":"Cerebrovasc. Brain Metab. Rev."},{"key":"90252_CR41","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/0304-3940(94)90684-X","volume":"172","author":"G Boka","year":"1994","unstructured":"Boka, G. et al. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson\u2019s disease. Neurosci. Lett. 172, 151\u2013154. https:\/\/doi.org\/10.1016\/0304-3940(94)90684-X (1994).","journal-title":"Neurosci. Lett."},{"key":"90252_CR42","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1152\/jn.00288.2003","volume":"90","author":"CC Hegg","year":"2003","unstructured":"Hegg, C. C., Au, E., Roskams, A. J. & Lucero, M. T. PACAP is present in the olfactory system and evokes calcium transients in olfactory receptor neurons. J. Neurophysiol. 90, 2711\u20132719. https:\/\/doi.org\/10.1152\/jn.00288.2003 (2003).","journal-title":"J. Neurophysiol."},{"key":"90252_CR43","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.mcn.2010.07.007","volume":"45","author":"S Kanekar","year":"2010","unstructured":"Kanekar, S., Gandham, M. & Lucero, M. T. PACAP protects against TNFalpha-induced cell death in olfactory epithelium and olfactory placodal cell lines. Mol. Cell Neurosci. 45, 345\u2013354. https:\/\/doi.org\/10.1016\/j.mcn.2010.07.007 (2010).","journal-title":"Mol. Cell Neurosci."},{"key":"90252_CR44","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s10194-018-0845-3","volume":"19","author":"D Reglodi","year":"2018","unstructured":"Reglodi, D., Vaczy, A., Rubio-Beltran, E. & MaassenVanDenBrink, A. Protective effects of PACAP in ischemia. J. Headache Pain 19, 19. https:\/\/doi.org\/10.1186\/s10194-018-0845-3 (2018).","journal-title":"J. Headache Pain"},{"key":"90252_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8091488","author":"V Denes","year":"2019","unstructured":"Denes, V., Geck, P., Mester, A. & Gabriel, R. Pituitary adenylate cyclase-activating polypeptide: 30 years in research spotlight and 600 million years in service. J. Clin. Med. https:\/\/doi.org\/10.3390\/jcm8091488 (2019).","journal-title":"J. Clin. Med."},{"key":"90252_CR46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00539","author":"PA Ottum","year":"2015","unstructured":"Ottum, P. A., Arellano, G., Reyes, L. I., Iruretagoyena, M. & Naves, R. Opposing roles of interferon-gamma on cells of the central nervous system in autoimmune neuroinflammation. Frontiers Immunol. https:\/\/doi.org\/10.3389\/fimmu.2015.00539 (2015).","journal-title":"Frontiers Immunol."},{"key":"90252_CR47","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/(sici)1098-1136(199703)19:3<227::Aid-glia5>3.0.Co;2-w","volume":"19","author":"MA Klein","year":"1997","unstructured":"Klein, M. A. et al. Impaired neuroglial activation in interleukin-6 deficient mice. Glia 19, 227\u2013233. https:\/\/doi.org\/10.1002\/(sici)1098-1136(199703)19:3%3c227::Aid-glia5%3e3.0.Co;2-w (1997).","journal-title":"Glia"},{"key":"90252_CR48","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1084\/jem.183.6.2627","volume":"183","author":"H Hirota","year":"1996","unstructured":"Hirota, H., Kiyama, H., Kishimoto, T. & Taga, T. Accelerated Nerve Regeneration in Mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma. J. Exp. Med. 183, 2627\u20132634. https:\/\/doi.org\/10.1084\/jem.183.6.2627 (1996).","journal-title":"J. Exp. Med."},{"key":"90252_CR49","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1002\/cne.1193","volume":"435","author":"B Nan","year":"2001","unstructured":"Nan, B., Getchell, M. L., Partin, J. V. & Getchell, T. V. Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. J. Comp. Neurol. 435, 60\u201377. https:\/\/doi.org\/10.1002\/cne.1193 (2001).","journal-title":"J. Comp. Neurol."},{"key":"90252_CR50","doi-asserted-by":"publisher","first-page":"2681","DOI":"10.1128\/IAI.00361-16","volume":"84","author":"JA St John","year":"2016","unstructured":"St John, J. A. et al. Burkholderia pseudomallei rapidly infects the brain stem and spinal cord via the trigeminal nerve after intranasal inoculation. Infect. Immun. 84, 2681\u20132688. https:\/\/doi.org\/10.1128\/IAI.00361-16 (2016).","journal-title":"Infect. Immun."},{"key":"90252_CR51","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/AIA.0b013e318034194e","volume":"45","author":"J-M Zhang","year":"2007","unstructured":"Zhang, J.-M. & An, J. Cytokines, inflammation, and pain. Int. Anesthesiol. Clin. 45, 27\u201337. https:\/\/doi.org\/10.1097\/AIA.0b013e318034194e (2007).","journal-title":"Int. Anesthesiol. Clin."},{"key":"90252_CR52","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.4049\/jimmunol.153.6.2618","volume":"153","author":"S Florquin","year":"1994","unstructured":"Florquin, S., Amraoui, Z., Abramowicz, D. & Goldman, M. Systemic release and protective role of IL-10 in staphylococcal enterotoxin B-induced shock in mice. J. Immunol. 153, 2618 (1994).","journal-title":"J. Immunol."},{"key":"90252_CR53","doi-asserted-by":"publisher","first-page":"4002","DOI":"10.1128\/iai.00176-09","volume":"77","author":"Y-L Cheng","year":"2009","unstructured":"Cheng, Y.-L. et al. Staphylococcus aureus induces microglial inflammation via a glycogen synthase kinase 3\u03b2-regulated pathway. Infect. Immun. 77, 4002\u20134008. https:\/\/doi.org\/10.1128\/iai.00176-09 (2009).","journal-title":"Infect. Immun."},{"key":"90252_CR54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00491","author":"G Arango Duque","year":"2014","unstructured":"Arango Duque, G. & Descoteaux, A. Macrophage cytokines: involvement in immunity and infectious diseases. Frontiers Immunol. https:\/\/doi.org\/10.3389\/fimmu.2014.00491 (2014).","journal-title":"Frontiers Immunol."},{"key":"90252_CR55","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1182\/blood.V90.3.909","volume":"90","author":"BJ Rollins","year":"1997","unstructured":"Rollins, B. J. Chemokines. Blood 90, 909\u2013928 (1997).","journal-title":"Blood"},{"key":"90252_CR56","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.4049\/jimmunol.156.8.3017","volume":"156","author":"JW Berman","year":"1996","unstructured":"Berman, J. W., Guida, M. P., Warren, J., Amat, J. & Brosnan, C. F. Localization of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat. J. Immunol. 156, 3017\u20133023 (1996).","journal-title":"J. Immunol."},{"key":"90252_CR57","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1046\/j.1365-2249.1998.00698.x","volume":"114","author":"CM Mastroianni","year":"1998","unstructured":"Mastroianni, C. M. et al. Chemokine profiles in the cerebrospinal fluid (CSF) during the course of pyogenic and tuberculous meningitis. Clin. Exp. Immunol. 114, 210\u2013214. https:\/\/doi.org\/10.1046\/j.1365-2249.1998.00698.x (1998).","journal-title":"Clin. Exp. Immunol."},{"key":"90252_CR58","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1086\/427514","volume":"191","author":"A-SW M\u00f8ller","year":"2005","unstructured":"M\u00f8ller, A.-S.W. et al. Chemokine patterns in meningococcal disease. J. Infect. Dis. 191, 768\u2013775. https:\/\/doi.org\/10.1086\/427514 (2005).","journal-title":"J. Infect. Dis."},{"key":"90252_CR59","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3389\/fnmol.2017.00191","volume":"10","author":"C Arcuri","year":"2017","unstructured":"Arcuri, C., Mecca, C., Bianchi, R., Giambanco, I. & Donato, R. The pathophysiological role of microglia in dynamic surveillance, phagocytosis and structural remodeling of the developing CNS. Front. Mol. Neurosci. 10, 191\u2013191. https:\/\/doi.org\/10.3389\/fnmol.2017.00191 (2017).","journal-title":"Front. Mol. Neurosci."},{"key":"90252_CR60","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/glia.20195","volume":"51","author":"AJ Vincent","year":"2005","unstructured":"Vincent, A. J., Taylor, J. M., Choi-Lundberg, D. L., West, A. K. & Chuah, M. I. Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes. Glia 51, 132\u2013147. https:\/\/doi.org\/10.1002\/glia.20195 (2005).","journal-title":"Glia"},{"key":"90252_CR61","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/ncpneuro0447","volume":"3","author":"SC Barnett","year":"2007","unstructured":"Barnett, S. C. & Riddell, J. S. Olfactory ensheathing cell transplantation as a strategy for spinal cord repair\u2014what can it achieve?. Nat. Clin. Pract. Neurol. 3, 152\u2013161. https:\/\/doi.org\/10.1038\/ncpneuro0447 (2007).","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"90252_CR62","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1002\/glia.23282","volume":"66","author":"RM Gomez","year":"2018","unstructured":"Gomez, R. M. et al. Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs). Glia 66, 1267\u20131301. https:\/\/doi.org\/10.1002\/glia.23282 (2018).","journal-title":"Glia"},{"key":"90252_CR63","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.expneurol.2010.08.012","volume":"229","author":"MI Chuah","year":"2011","unstructured":"Chuah, M. I., Hale, D. M. & West, A. K. Interaction of olfactory ensheathing cells with other cell types in vitro and after transplantation: glial scars and inflammation. Exp. Neurol. 229, 46\u201353. https:\/\/doi.org\/10.1016\/j.expneurol.2010.08.012 (2011).","journal-title":"Exp. Neurol."},{"key":"90252_CR64","doi-asserted-by":"publisher","first-page":"10240","DOI":"10.1038\/s41598-018-28551-2","volume":"8","author":"M Chen","year":"2018","unstructured":"Chen, M. et al. The serrulatane diterpenoid natural products RAD288 and RAD289 stimulate properties of olfactory ensheathing cells useful for neural repair therapies. Sci. Rep. 8, 10240. https:\/\/doi.org\/10.1038\/s41598-018-28551-2 (2018).","journal-title":"Sci. Rep."},{"key":"90252_CR65","doi-asserted-by":"publisher","first-page":"e111787","DOI":"10.1371\/journal.pone.0111787","volume":"9","author":"J Tello Velasquez","year":"2014","unstructured":"Tello Velasquez, J. et al. Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells. PLoS ONE 9, e111787. https:\/\/doi.org\/10.1371\/journal.pone.0111787 (2014).","journal-title":"PLoS ONE"},{"key":"90252_CR66","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s13311-016-0485-8","volume":"14","author":"DJ Hao","year":"2017","unstructured":"Hao, D. J. et al. Lipopolysaccharide and curcumin co-stimulation potentiates olfactory ensheathing cell phagocytosis via enhancing their activation. Neurotherapeutics 14, 502\u2013518. https:\/\/doi.org\/10.1007\/s13311-016-0485-8 (2017).","journal-title":"Neurotherapeutics"},{"key":"90252_CR67","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1177\/0963689718759472","volume":"27","author":"AA Wright","year":"2018","unstructured":"Wright, A. A. et al. Enhancing the therapeutic potential of olfactory ensheathing cells in spinal cord repair using neurotrophins. Cell Transplant. 27, 867\u2013878. https:\/\/doi.org\/10.1177\/0963689718759472 (2018).","journal-title":"Cell Transplant."},{"key":"90252_CR68","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/s41598-020-57793-2","volume":"10","author":"M Chen","year":"2020","unstructured":"Chen, M. et al. The plant natural product 2-methoxy-1,4-naphthoquinone stimulates therapeutic neural repair properties of olfactory ensheathing cells. Sci. Rep. 10, 951. https:\/\/doi.org\/10.1038\/s41598-020-57793-2 (2020).","journal-title":"Sci. Rep."},{"key":"90252_CR69","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1002\/glia.20586","volume":"55","author":"LC Windus","year":"2007","unstructured":"Windus, L. C., Claxton, C., Allen, C. L., Key, B. & St John, J. A. Motile membrane protrusions regulate cell-cell adhesion and migration of olfactory ensheathing glia. Glia 55, 1708\u20131719. https:\/\/doi.org\/10.1002\/glia.20586 (2007).","journal-title":"Glia"},{"key":"90252_CR70","doi-asserted-by":"publisher","DOI":"10.3791\/50079","author":"S Schildge","year":"2013","unstructured":"Schildge, S., Bohrer, C., Beck, K. & Schachtrup, C. Isolation and culture of mouse cortical astrocytes. J. Vis. Exp. https:\/\/doi.org\/10.3791\/50079 (2013).","journal-title":"J. Vis. Exp."},{"key":"90252_CR71","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1002\/cpns.71","volume":"88","author":"LM Holt","year":"2019","unstructured":"Holt, L. M., Stoyanof, S. T. & Olsen, M. L. Magnetic cell sorting for in vivo and in vitro astrocyte, neuron, and microglia analysis. Curr. Protoc. Neurosci. 88, e71. https:\/\/doi.org\/10.1002\/cpns.71 (2019).","journal-title":"Curr. Protoc. Neurosci."},{"key":"90252_CR72","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc09c01s28","author":"DM Missiakas","year":"2013","unstructured":"Missiakas, D. M. & Schneewind, O. Growth and laboratory maintenance of Staphylococcus aureus. Curr. Protoc. Microbiol. https:\/\/doi.org\/10.1002\/9780471729259.mc09c01s28 (2013).","journal-title":"Curr. Protoc. Microbiol."},{"key":"90252_CR73","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1002\/glia.22644","volume":"62","author":"ID Cooley","year":"2014","unstructured":"Cooley, I. D., Chauhan, V. S., Donneyz, M. A. & Marriott, I. Astrocytes produce IL-19 in response to bacterial challenge and are sensitive to the immunosuppressive effects of this IL-10 family member. Glia 62, 818\u2013828. https:\/\/doi.org\/10.1002\/glia.22644 (2014).","journal-title":"Glia"},{"key":"90252_CR74","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.3389\/fmicb.2017.01354","volume":"8","author":"G Rollin","year":"2017","unstructured":"Rollin, G. et al. Intracellular survival of Staphylococcus aureus in endothelial cells: a matter of growth or persistence. Front Microbiol. 8, 1354\u20131354. https:\/\/doi.org\/10.3389\/fmicb.2017.01354 (2017).","journal-title":"Front Microbiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90252-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90252-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90252-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:36:30Z","timestamp":1699058190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90252-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["90252"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-90252-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,21]]},"assertion":[{"value":"2 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10722"}}