{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:05:44Z","timestamp":1791453944538,"version":"4.3.3"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Streptococcus agalactiae (Sta) of Lancefield group B is the primary etiological agent of bacterial meningitis in Nile tilapia and newborn humans. Thus, the study of this disease is of fundamental importance for aquaculture and human medicine. Additionally, elucidation of the mechanisms involved in the host\u2013pathogenic response is important for the success of new therapies. In the present study, we elucidated important aspects of the innate immune response in the brain tissue of Nile tilapia (Oreochromis niloticus) infected by Sta. The neuroinflammatory process in the meninges started with the migration of MHC class II and CD68 + cells, production of TNF-alpha, and the effective immune response to Sta was mediated by the increased iNOs+. In conclusion, the present study brings a partial understanding of the pathophysiological and neuroinflammatory mechanisms in meningitis in Sta infected tilapia, enabling important advances in the therapy of this disease as well as the possibility of using this biological model to understand human meningitis.<\/jats:p>","DOI":"10.3390\/ani10112166","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T09:46:18Z","timestamp":1605865578000},"page":"2166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Meningitis Caused by Streptococcus agalactiae in Nile Tilapia (Oreochromis niloticus): Infection and Inflammatory Response"],"prefix":"10.3390","volume":"10","author":[{"given":"Silas Fernandes","family":"Eto","sequence":"first","affiliation":[{"name":"Department of Postgraduate in Health Sciences-PROCISA, Federal University of Roraima (UFRR), Boa Vista 69310-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayanne Carla","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra Cristina de","family":"Moraes","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Federal University of Rond\u00f4nia (UNIR), Rond\u00f4nia 76801-058, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7449-0116","authenticated-orcid":false,"given":"Jo\u00e3o Victor da Costa","family":"Alecrim","sequence":"additional","affiliation":[{"name":"Department of Postgraduate in Health Sciences-PROCISA, Federal University of Roraima (UFRR), Boa Vista 69310-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Galdino de","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Postgraduate in Health Sciences-PROCISA, Federal University of Roraima (UFRR), Boa Vista 69310-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fab\u00edola Christian Almeida de","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Postgraduate in Health Sciences-PROCISA, Federal University of Roraima (UFRR), Boa Vista 69310-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7572-2767","authenticated-orcid":false,"given":"Ives","family":"Charlie-Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, ICB-USP, S\u00e3o Paulo 01222-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-3940","authenticated-orcid":false,"given":"Marco Antonio de Andrade","family":"Belo","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine of Unesp, School of Agrarian and Veterinary Sciences, Sao Paulo State University (Unesp), Jaboticabal 14884-900, Brazil"},{"name":"Laboratory of Animal Pharmacology and Toxicology, University of Brazil, Descalvado 13690-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Martins","family":"Pizauro","sequence":"additional","affiliation":[{"name":"Department of Technology, School of Agrarian and Veterinary Sciences, Sao Paulo State University (Unesp), Jaboticabal 14884-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.mimet.2009.11.010","article-title":"A multiplex PCR assay for the direct identification of the capsular type (Ia to IX) of Streptococcus agalactiae","volume":"80","author":"Imperi","year":"2010","journal-title":"J. Microbiol. Methods"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1128\/JCM.01471-13","article-title":"Discrimination of enterohemorrhagic Escherichia coli (EHEC) from non-EHEC strains based on detection of various combinations of type III effector genes","volume":"51","author":"Delannoy","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.56808\/2985-1130.2376","article-title":"Duplex PCR for simultaneous and unambiguous detection of Streptococcus iniae and Streptococcus agalactiae associated with streptococcosis of cultured tilapia in Thailand","volume":"42","author":"Rodkhum","year":"2012","journal-title":"Thai. J. Vet. Med."},{"key":"ref_4","unstructured":"FAO (2014). The State of World Fisheries and Aquaculture, FAO."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"El-Sayed, A.F.M. (2006). Tilapia Culture, Academic Press.","DOI":"10.1079\/9780851990149.0000"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.vetmic.2013.09.001","article-title":"Rare serotype occurrence and PFGE genotypic diversity of Streptococcus agalactiae isolated from tilapia in China","volume":"167","author":"Li","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.vetmic.2008.10.016","article-title":"Aspects of the natural history and virulence of S. agalactiae infection in Nile tilapia","volume":"136","author":"Mian","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yi, M., Wang, M., Li, Z., Liu, Z., Song, C., Zhang, D., Gao, F., Ke, X., Cao, J., and Lu, M. (2019). An investigation into the effects of Streptococcus agalactiae on the 5-HT system and the behavior of GIFT tilapia (Oreochromis niloticus). Aquaculture Rep., 15.","DOI":"10.1016\/j.aqrep.2019.100232"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1017\/S1462399408000811","article-title":"Recent advances in understanding the molecular basis of group B Streptococcus virulence","volume":"10","author":"Maisey","year":"2008","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1742-2094-11-98","article-title":"Neuro-inflammation and M2 microglia: The good, the bad, and the inflamed","volume":"11","author":"Cherry","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/nan.12011","article-title":"Review: Activation patterns of microglia and their identification in the human brain","volume":"39","author":"Boche","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2990.2012.01306.x","article-title":"Microglia of the aged brain: Primed to be activated and resistant to regulation","volume":"39","author":"Norden","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_13","first-page":"652","article-title":"Direct Identification of Major Pathogens of the Bubaline Subclinical Mastitis in Egypt using PCR","volume":"6","author":"Abdelrahmanb","year":"2010","journal-title":"Am. J. Sci"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.fsi.2018.02.048","article-title":"Validation of IgY for the diagnosis of Streptococcus agalactiae-caused endocarditis and bacterial meningitis in Nile tilapia (Oreochromis niloticus)","volume":"76","author":"Eto","year":"2018","journal-title":"Fish. Shellfish. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1046\/j.1365-2761.1997.d01-105.x","article-title":"Lectin histochemical studies on Sphaerospora sp. (Myxozoa) from Italian brown trout, Salmo trutta L.","volume":"20","author":"Bovo","year":"1997","journal-title":"J. Fish. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Varghese, F., Bukhari, A.B., Malhotra, R., and De, A. (2014). IHC Profiler: An open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096801"},{"key":"ref_17","unstructured":"Snedecor, G.W., and Cochran, W.G. (1974). Statistical Methods, Iowa State University Press."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"561","DOI":"10.7589\/0090-3558-42.3.561","article-title":"First report of Streptococcus agalactiae and Lactococcus garvieae from a wild bottlenose dolphin (Tursiops truncatus)","volume":"42","author":"Evans","year":"2006","journal-title":"J. Wildl. Dis."},{"key":"ref_19","first-page":"2640","article-title":"Streptococcus agalactiae the etiological agent of mass mortality in farmed red tilapia (Oreochromis sp.)","volume":"20","author":"Abuseliana","year":"2010","journal-title":"J. Anim. Vet. Adv."},{"key":"ref_20","first-page":"74","article-title":"First report of Streptococcus agalactiae isolated from Oreochromis niloticus in Piura, Peru: Molecular identification and histopathological lesions","volume":"4","author":"Asencios","year":"2016","journal-title":"Aquacult. Rep."},{"key":"ref_21","unstructured":"World Health Organization (WHO) (2017, November 09). Meningococcal Meningitis: Fact Sheet. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs141\/en\/."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Barichello, T., Generoso, J.S., Sim\u00f5es, L.R., Elias, S.G., and Quevedo, J. (2013). Role of oxidative stress in the pathophysiology of pneumococcal meningitis. Oxid. Med. Cell. Longev., 371465.","DOI":"10.1155\/2013\/371465"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1111\/j.1469-0691.2011.03576.x","article-title":"Neonatal group B streptococcal disease: From pathogenesis to preventive strategies","volume":"17","author":"Melin","year":"2011","journal-title":"Clin. Microbiol. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/j.1365-2958.2006.05406.x","article-title":"The Group B Streptococcus NADH oxidase Nox-2 is involved in fatty acid biosynthesis during aerobic growth and contributes to virulence","volume":"62","author":"Yamamoto","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1093\/infdis\/jiw268","article-title":"Thioredoxins and Methionine Sulfoxide Reductases in the Pathophysiology of Pneumococcal Meningitis","volume":"214","author":"Ribes","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.cell.2008.04.037","article-title":"Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo","volume":"133","author":"Peri","year":"2008","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.dci.2012.07.007","article-title":"Adult zebrafish model of bacterial meningitis in Streptococcus agalactiae infection","volume":"38","author":"Patterson","year":"2012","journal-title":"Dev. Comp. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.aquaculture.2018.10.045","article-title":"Immunoglobulin Y in the diagnosis of Aeromonas hydrophila infection in Nile tilapia (Oreochromis niloticus)","volume":"500","author":"Fernandes","year":"2019","journal-title":"Aquaculture"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1038\/s41598-019-41312-z","article-title":"Acute-phase proteins during inflammatory reaction by bacterial infection: Fish-model","volume":"9","author":"Klein","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1111\/are.14499","article-title":"Maternal immunity of tilapia broodstock vaccinated with polyvalent vaccine and resistance of their offspring against Streptococcus agalactiae","volume":"51","author":"Nurani","year":"2020","journal-title":"Aquacult. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrmicro1952","article-title":"Mechanisms of microbial traversal of the blood-brain barrier","volume":"6","author":"Kim","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Santiago-Tirado, F.H., Onken, M.D., Cooper, J.A., Klein, R.S., and Doering, T.L. (2017). Trojan horse transit contributes to blood-brain barrier crossing of a eukaryotic pathogen. mBio, 8.","DOI":"10.1128\/mBio.02183-16"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1128\/IAI.71.5.2318-2325.2003","article-title":"Trojan horse effect: Phagocyte-mediated Streptococcus iniae infection of fish","volume":"71","author":"Zlotkin","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_34","unstructured":"Abbas, A.K., Lichtman, A.H., and Pillai, S. (2010). Cellular and Molecular Immunology, Saunders\/Elsevier."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1227\/01.NEU.0000170440.32720.77","article-title":"CD68 and CR3\/43 immunohistochemical expression in secretory meningiomas","volume":"57","author":"Caffo","year":"2005","journal-title":"Neurosurgery"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-2094-4-4","article-title":"Microglia activation in sepsis: A case-control study","volume":"4","author":"Lemstra","year":"2007","journal-title":"J. Neuroinflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/jnr.20663","article-title":"Responses of microglia in vitro to the gram-positive bacterial component, lipoteichoic acid","volume":"82","author":"Yeh","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jneuroim.2005.01.015","article-title":"Autocrine activation of microglia by tumor necrosis factor-alpha","volume":"162","author":"Kuno","year":"2005","journal-title":"J. Neuroimmunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Olmos, G., and Llado, J. (2014). Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity. Mediat. Inflamm., 861231.","DOI":"10.1155\/2014\/861231"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/cercor\/bhg108","article-title":"Involvement of tumor necrosis factor alpha in hippocampal development and function","volume":"14","author":"Golan","year":"2004","journal-title":"Cereb. Cortex"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/neu.1064","article-title":"Neuronal localization of the TNF\u03b1 converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques","volume":"49","author":"Skovronsky","year":"2001","journal-title":"J. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1128\/AAC.02432-15","article-title":"Low concentrations of nitric oxide modulate Streptococcus pneumoniae biofilm metabolism and antibiotic tolerance","volume":"60","author":"Allan","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1086\/514226","article-title":"Inducible Nitric Oxide Synthase and the Effect of Aminoguanidine in Experimental Neonatal Meningitis","volume":"177","author":"Leib","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_44","first-page":"893","article-title":"Burden of disease caused by Streptococcus pneumoni in childrens younger than 5 years: Global estimates","volume":"12","author":"Wolfson","year":"2009","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00401-015-1531-z","article-title":"Host-pathogen interactions in bacterial meningitis","volume":"131","author":"Doran","year":"2016","journal-title":"Acta Neuropathol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/10\/11\/2166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:35:02Z","timestamp":1760178902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/10\/11\/2166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,20]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ani10112166"],"URL":"https:\/\/doi.org\/10.3390\/ani10112166","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,20]]}}}