{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:23:41Z","timestamp":1791386621479,"version":"4.3.3"},"reference-count":143,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Free-living amoebas, including Acanthamoeba spp., are widely distributed in soil, water, and air. They are capable of causing granulomatous amebic encephalitis, Acanthamoeba pneumonia, Acanthamoeba keratitis, and disseminated acanthamoebiasis. Despite low occurrence worldwide, the mortality rate of Acanthamoeba spp. infections is very high, especially in immunosuppressed hosts. Acanthamoeba infections are a medical problem, owing to limited improvement in diagnostics and treatment, which is associated with incomplete knowledge of pathophysiology, pathogenesis, and the host immune response against Acanthamoeba spp. infection. The aim of this review is to present the biochemical and molecular mechanisms of Acanthamoeba spp.\u2013host interactions, including the expression of Toll-like receptors, mechanisms of an immune response, the activity of metalloproteinases, the secretion of antioxidant enzymes, and the expression and activity of cyclooxygenases. We show the relationship between Acanthamoeba spp. and the host at the cellular level and host defense reactions that lead to changes in the selected host\u2019s organs.<\/jats:p>","DOI":"10.3390\/ijms22031261","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T12:20:26Z","timestamp":1611750026000},"page":"1261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Immunopathogenicity of Acanthamoeba spp. in the Brain and Lungs"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0051-2295","authenticated-orcid":false,"given":"Karolina","family":"Kot","sequence":"first","affiliation":[{"name":"Department of Biology and Medical Parasitology, Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"\u0141anocha-Arendarczyk","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Parasitology, Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-5493","authenticated-orcid":false,"given":"Danuta","family":"Kosik-Bogacka","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Pharmaceutical Botany, Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.scitotenv.2017.01.046","article-title":"Detection of Acanthamoeba spp. in water samples collected from natural water reservoirs, sewages, and pharmaceutical factory drains using LAMP and PCR in China","volume":"584\u2013585","author":"Lass","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1128\/CMR.16.2.273-307.2003","article-title":"Acanthamoeba spp. as agents of disease in humans","volume":"16","author":"Cabral","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.clae.2017.12.017","article-title":"Acanthamoeba in the eye, can the parasite hide even more? Latest developments on the disease","volume":"41","author":"Cid","year":"2018","journal-title":"Cont. Lens. Anterior Eye"},{"key":"ref_4","first-page":"299","article-title":"Amoebas from the genus Acanthamoeba and their pathogenic properties","volume":"64","author":"Kot","year":"2018","journal-title":"Ann. Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107788","DOI":"10.1016\/j.exppara.2019.107788","article-title":"Acanthamoeba and its pathogenic role in granulomatous amebic encephalitis","volume":"208","author":"Kalra","year":"2020","journal-title":"Exp. Parasitol."},{"key":"ref_6","first-page":"2","article-title":"Role of Acanthamoeba in granulomatous encephalitis: A review","volume":"1","author":"Duggal","year":"2017","journal-title":"J. Infect. Dis. Immune Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4103\/2229-5070.149889","article-title":"Management of granulomatous amebic encephalitis: Laboratory diagnosis and treatment","volume":"5","author":"Parija","year":"2015","journal-title":"Trop. Parasitol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1051\/parasite\/2015010","article-title":"An update on Acanthamoeba keratitis: Diagnosis, pathogenesis and treatment","volume":"22","author":"Khan","year":"2015","journal-title":"Parasite"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1574-6976.2006.00023.x","article-title":"Acanthamoeba: Biology and increasing importance in human health","volume":"30","author":"Khan","year":"2006","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.pt.2013.01.006","article-title":"Acanthamoeba keratitis: An emerging disease gathering importance worldwide?","volume":"29","author":"Valladares","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/B978-0-444-53490-3.00010-8","article-title":"Infections with free-living amebae","volume":"114","author":"Visvesvara","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jiph.2017.09.013","article-title":"Acanthamoeba keratitis in noncompliant soft contact lenses users: Genotyping and risk factors, a study from Cairo, Egypt","volume":"11","author":"Taher","year":"2018","journal-title":"J. Infect. Public Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4103\/ijmr.IJMR_1564_17","article-title":"Genotyping of Acanthamoeba spp. isolated from patients with granulomatous amoebic encephalitis","volume":"148","author":"Megha","year":"2018","journal-title":"Indian J. Med. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1550-7408.1996.tb04510.x","article-title":"Subgenus systematics of Acanthamoeba: Four nuclear 18S rDNA sequence types","volume":"43","author":"Gast","year":"1996","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/jeu.12186","article-title":"Phylogenetic analysis and the evolution of the 18S rRNA gene typing system of Acanthamoeba","volume":"62","author":"Fuerst","year":"2015","journal-title":"J. Eukaryot. Microbiol"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fuerst, P.A., and Booton, G.C. (2020). Species, Sequence Types and Alleles: Dissecting Genetic Variation in Acanthamoeba. Pathogens, 9.","DOI":"10.3390\/pathogens9070534"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1128\/JCM.40.5.1621-1625.2002","article-title":"18S ribosomal DNA typing and tracking of Acanthamoeba species isolates from corneal scrape specimens, contact lenses, lens cases, and home water supplies of Acanthamoeba keratitis patients in Hong Kong","volume":"40","author":"Booton","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1756-3305-5-6","article-title":"Biology and pathogenesis of Acanthamoeba","volume":"10","author":"Siddiqui","year":"2012","journal-title":"Parasit. Vectors"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1099\/jmm.0.000234","article-title":"Genotyping of Acanthamoeba spp. and characterization of the prevalent T4 type along with T10 and unassigned genotypes from amoebic keratitis patients in India","volume":"65","author":"Behera","year":"2016","journal-title":"J. Med. Microbiol."},{"key":"ref_20","first-page":"271","article-title":"The occurence Acanthamoeba (Free Living Amoeba) in environmental and respiratory samples in Poland","volume":"48","author":"Maciejewska","year":"2009","journal-title":"Acta Protozool."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.3201\/eid1411.070854","article-title":"Successful treatment of disseminated Acanthamoeba sp. infection with miltefosine","volume":"14","author":"Aichelburg","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"736","DOI":"10.3201\/eid1305.061347","article-title":"Fatal disseminated Acanthamoeba lenticulata infection in a heart transplant patient","volume":"13","author":"Barete","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13000-018-0706-z","article-title":"A case report of granulomatous amoebic encephalitis by Group 1 Acanthamoeba genotype T18 diagnosed by the combination of morphological examination and genetic analysis","volume":"13","author":"Matsui","year":"2018","journal-title":"Diagn. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1007\/s00436-018-5997-1","article-title":"DNA extraction from amoebal isolates and genotype determination of Acanthamoeba from tap water in Latvia","volume":"117","author":"Trofimova","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.exppara.2017.09.016","article-title":"Molecular identification of waterborne free living amoebae (Acanthamoeba, Naegleria and Vermamoeba) isolated from municipal drinking water and environmental sources, Semnan province, north half of Iran","volume":"183","author":"Javanmard","year":"2017","journal-title":"Exp. Parasitol."},{"key":"ref_26","first-page":"147","article-title":"The occurrence of free-living amoebae in fountains","volume":"94","author":"Derda","year":"2013","journal-title":"Probl. Hig. Epidemiol."},{"key":"ref_27","first-page":"161","article-title":"Histological studies of selected organs of mice experimentally infected with Acanthamoeba spp.","volume":"64","year":"2005","journal-title":"Folia Morphol."},{"key":"ref_28","first-page":"106","article-title":"Pathogenic free-living amoeba","volume":"1","author":"Galant","year":"2017","journal-title":"Post Mikrobiol."},{"key":"ref_29","first-page":"484","article-title":"Advances in the diagnosis and treatment of Acanthamoeba keratitis","volume":"2012","author":"Clarke","year":"2012","journal-title":"J. Ophthal Mol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.exppara.2008.11.009","article-title":"Acanthamoeba castellanii: High antibody prevalence in racially and ethnically diverse populations","volume":"121","author":"Brindley","year":"2009","journal-title":"Exp. Parasitol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4103\/2152-7806.132239","article-title":"Acanthamoeba encephalitis: A Case Report and Review of Therapy","volume":"5","author":"Zamora","year":"2014","journal-title":"Surg. Neurol. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00436-007-0749-7","article-title":"Demonstration of Balamuthia and Acanthamoeba mitochondrial DNA in sectioned archival brain and other tissues by the polymerase chain reaction","volume":"102","author":"Yagi","year":"2008","journal-title":"Parasitol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1440-1789.2010.01151.x","article-title":"Acanthamoeba meningoencephalitis in an immunocompetent patient: An autopsy case report","volume":"31","author":"Reddy","year":"2011","journal-title":"Neuropathology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.patbio.2012.03.002","article-title":"Pathogenic free-living amoebe: Epidemiology and clinical review","volume":"60","author":"Trabelsi","year":"2012","journal-title":"Pathol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/clind\/13.Supplement_5.S399","article-title":"Infection of the central nervous system due to Acanthamoeba","volume":"13","author":"Martinez","year":"1991","journal-title":"Rev. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.4103\/jfmpc.jfmpc_1010_19","article-title":"Acanthamoeba encephalitis in immunocompetent hosts: A report of two cases","volume":"9","author":"Das","year":"2020","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4103\/2229-5070.138540","article-title":"Acanthamoeba meningoencephalitis in immunocompetent: A case report and review of literature","volume":"4","author":"Khanna","year":"2014","journal-title":"Trop. Parasitol."},{"key":"ref_38","first-page":"bcr2012007449","article-title":"Central nervous system infection with Acanthamoeba in a malnourished child","volume":"2012","author":"Khurana","year":"2012","journal-title":"Case Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.surneu.2008.04.008","article-title":"Acanthamoeba infection in an interhemispheric ependymal cyst: A case report","volume":"72","author":"Ranjan","year":"2009","journal-title":"Surg. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"601","DOI":"10.4103\/IJPM.IJPM_815_16","article-title":"Opportunistic free: Living amoeba now becoming a usual pathogen?","volume":"60","author":"Ghadage","year":"2017","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_41","first-page":"484","article-title":"Acanthameba meningoencephalitis: A case report","volume":"50","author":"Hamide","year":"2002","journal-title":"Neurol. India"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s12098-009-0205-z","article-title":"Acanthameba meningitis with successful outcome","volume":"76","author":"Saxena","year":"2009","journal-title":"Indian J. Pediatr."},{"key":"ref_43","first-page":"179","article-title":"Acanthamoeba encephalitis in an immunocompeteny child and review of the imaging features of intracranical acanthamoebic infections in immunocompetent patients","volume":"23","author":"Hanafiah","year":"2018","journal-title":"Neurol. Asia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1128\/JCM.38.10.3892-3895.2000","article-title":"Granulomatous amebic encephalitis in a patient with AIDS: Isolation of acanthamoeba sp. Group II from brain tissue and successful treatment with sulfadiazine and fluconazole","volume":"38","author":"Santiago","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1128\/JCM.44.5.1903-1904.2006","article-title":"Early diagnosis of Acanthamoeba infection during routine cytological examination of cerebrospinal fluid","volume":"44","author":"Petry","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1002\/lt.21409","article-title":"Cure of Acanthamoeba cerebral abscess in a liver transplant patient","volume":"14","author":"Fung","year":"2008","journal-title":"Liver Transpl."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1128\/JCM.01456-10","article-title":"Granulomatous amebic encephalitis in a child with acute lymphoblastic leukemia successfully treated with multimodal antimicrobial therapy and hyperbaric oxygen","volume":"49","author":"Maritschnegg","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12028-009-9291-z","article-title":"Acute granulomatous acanthamoeba encephalitis in an immunocompetent patient","volume":"12","author":"Lackner","year":"2010","journal-title":"Neurocrit. Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1128\/JCM.01177-07","article-title":"Granulomatous amoebic encephalitis caused by Acanthamoeba amoebae of genotype T2 in a human immunodeficiency virus-negative patient","volume":"46","author":"Walochnik","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s15010-018-1231-4","article-title":"Non-granulomatous cerebellar infection by Acanthamoeba spp. in an immunocompetent host","volume":"46","author":"Modica","year":"2018","journal-title":"Infection"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s15010-017-1037-9","article-title":"Survival of an AIDS patient after infection with Acanthamoeba sp. of the central nervous system","volume":"45","author":"Udayamurthy","year":"2017","journal-title":"Infection"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4269\/ajtmh.2012.12-0100","article-title":"Treatment of granulomatous amoebic encephalitis with voriconazole and miltefosine in an immunocompetent soldier","volume":"87","author":"Webster","year":"2012","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4269\/ajtmh.2009.81.277","article-title":"First case of granulomatous amebic encephalitis caused by Acanthamoeba castellanii in Taiwan","volume":"81","author":"Sheng","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_54","unstructured":"Kasprzak, W. (1985). Free-Living Amoeba with Pathogenic Properties to Human and Animals, Pa\u0144stwowe Wydawnictwo Naukowe. [1st ed.]."},{"key":"ref_55","unstructured":"Khan, N.A., and Siddiqui, R. (2011). The neuropathogenesis of Acanthamoeba encephalitis: Barriers to overcome. J. Cell Sci. Ther., S3."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"25S","DOI":"10.1111\/j.1550-7408.1990.tb01142.x","article-title":"Epidemiology of free-living ameba infections","volume":"37","author":"Visvesvara","year":"1990","journal-title":"J. Protozool."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s42269-019-0227-2","article-title":"Toll-like receptors activation, signaling, and targeting: An overview","volume":"43","author":"Sibaii","year":"2019","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.4049\/jimmunol.173.6.3916","article-title":"Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs","volume":"173","author":"Olson","year":"2004","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13798","DOI":"10.1073\/pnas.0702553104","article-title":"Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits","volume":"104","author":"Tang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1084\/jem.191.3.423","article-title":"Consequences of cell death: Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells","volume":"191","author":"Sauter","year":"2000","journal-title":"J. Exp. Med"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15107","DOI":"10.1074\/jbc.M111204200","article-title":"HSP70 as endogenous stimulus of the Toll\/interleukin-1 receptor signal pathway","volume":"277","author":"Vabulas","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1007\/s00436-016-5217-9","article-title":"Toll-like receptors in the brain of mice following infection with Acanthamoeba spp.","volume":"115","author":"Derda","year":"2016","journal-title":"Parasitol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"640","DOI":"10.3855\/jidc.2019","article-title":"T-cell response to bacterial agents","volume":"5","author":"Benagiano","year":"2011","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Shepherd, F.R., and McLaren, J.E. (2020). T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176144"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S1074-7613(02)00331-X","article-title":"Further checkpoints in Th1 development","volume":"16","author":"Robinson","year":"2002","journal-title":"Immunity"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/00001432-200306000-00003","article-title":"Toll-like receptors and T-helper-1\/T-helper-2 responses","volume":"16","author":"Dabbagh","year":"2003","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fouzder, C., Mukhuty, A., Das, S., and Chattopadhyay, D. (2019). TLR signaling on protozoan and helminthic parasite. Toll-Like Receptors, InTechOpen.","DOI":"10.5772\/intechopen.84711"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Massilamany, C., Marciano-Cabral, F., Rocha-Azevedo, B.d., Jamerson, M., Gangaplara, A., Steffen, D., Zabad, R., Illes, Z., Sobel, R.A., and Reddy, J. (2014). SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098506"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nri1418","article-title":"Matrix metalloproteinases as modulators of inflammation and innate immunity","volume":"4","author":"Parks","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.cellbio.17.1.463","article-title":"How matrix metalloproteinases regulate cell behavior","volume":"17","author":"Sternlicht","year":"2001","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Raeeszadeh-Sarmazdeh, M., Do, L.D., and Hritz, B.G. (2020). Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics. Cells, 9.","DOI":"10.3390\/cells9051313"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrn1807","article-title":"Metalloproteinases: Mediators of pathology and regeneration in the CNS","volume":"6","author":"Yong","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0166-2236(97)01169-7","article-title":"Matrix metalloproteinases and diseases of the CNS","volume":"21","author":"Yong","year":"1998","journal-title":"Trends Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.semcdb.2007.06.003","article-title":"MMPs in the central nervous system: Where the good guys go bad","volume":"19","author":"Agrawal","year":"2008","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3390\/pathogens2010105","article-title":"The significance of matrix metalloproteinases in parasitic infections involving the central nervous system","volume":"2","author":"Bruschi","year":"2013","journal-title":"Pathogens"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1099\/mic.0.000537","article-title":"Expression of matrix metalloproteinases in Naegleria fowleri and their role in invasion of the central nervous system","volume":"163","author":"Lam","year":"2017","journal-title":"Microbiology"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"\u0141anocha-Arendarczyk, N., Baranowska-Bosiacka, I., Gutowska, I., Kolasa-Wo\u0142osiuk, A., Kot, K., \u0141anocha, A., Metryka, E., Wiszniewska, B., Chlubek, D., and Kosik-Bogacka, D. (2018). The Activity of Matrix Metalloproteinases (MMP-2, MMP-9) and Their Tissue Inhibitors (TIMP-1, TIMP-3) in the Cerebral Cortex and Hippocampus in Experimental Acanthamoebiasis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124128"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.5114\/aoms.2015.56342","article-title":"Brain-derived neurotrophic factor and its clinical implications","volume":"11","author":"Bathina","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1006\/mcne.1998.0684","article-title":"Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb","volume":"11","author":"Zigova","year":"1998","journal-title":"Mol. Cell Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6718","DOI":"10.1523\/JNEUROSCI.21-17-06718.2001","article-title":"Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain","volume":"21","author":"Benraiss","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.yfrne.2006.09.003","article-title":"Estrogen-BDNF interactions: Implications for neurodegenerative diseases","volume":"27","author":"Sohrabji","year":"2006","journal-title":"Front. Neuroendocrinol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Palasz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., and Niewiadomska, G. (2020). BDNF as a Promising Therapeutic Agent in Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031170"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.phrs.2005.01.001","article-title":"Progressive loss of BDNF in a mouse model of Huntington\u2019s disease and rescue by BDNF delivery","volume":"52","author":"Zuccato","year":"2005","journal-title":"Pharmacol. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/INF.0000000000001382","article-title":"Brain-derived Neurotrophic Factor Is Associated with Disease Severity and Clinical Outcome in Ugandan Children Admitted to Hospital With Severe Malaria","volume":"36","author":"McDonald","year":"2017","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.bjid.2016.11.005","article-title":"Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis","volume":"21","author":"Cordeiro","year":"2017","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_87","unstructured":"\u0141anocha-Arendarczyk, N., Kosik-Bogacka, D., Kot, K., Baranowska-Bosiacka, I., and Metryka, E. (2018, January 8). Brain-derived neurotrophic factor (BDNF) in the brain cortex and hippocampus of mice infected with Acanthamoeba spp.. Proceedings of the Conference: Biotechnologia-Problemy i Wyzwania, Szczecin, Poland. Abstract book. (In Polish)."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/BF02532301","article-title":"Neurotrophin-4: The odd one out in the neurotrophin family","volume":"21","year":"1996","journal-title":"Neurochem. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s004010000268","article-title":"Brain-derived neurotrophic factor reduces cortical cell death by ischemia after middle cerebral artery occlusion in the rat","volume":"101","author":"Ferrer","year":"2001","journal-title":"Acta Neuropathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0959-4388(99)80028-2","article-title":"Synaptic plasticity in cortical systems","volume":"9","author":"Klintsova","year":"1999","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/BF02532298","article-title":"Neurotrophin-4\/5 treatment reduces infarct size in rats with middle cerebral artery occlusion","volume":"21","author":"Chan","year":"1996","journal-title":"Neurochem. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Chung, J.Y., Kim, M.W., Bang, M.S., and Kim, M. (2013). Increased expression of neurotrophin 4 following focal cerebral ischemia in adult rat brain with treadmill exercise. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0052461"},{"key":"ref_93","first-page":"117","article-title":"Activity of neurotrophin (NT-4) in the brain cortex and hippocampus in experimental acanthamoebiasis with regard to the immunological status of the host","volume":"65","author":"Kot","year":"2019","journal-title":"Ann. Parasitol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1126\/science.127.3313.1506","article-title":"Acanthamoeba: Observations on animal pathogenicity","volume":"127","author":"Culbertson","year":"1958","journal-title":"Science"},{"key":"ref_95","first-page":"185","article-title":"Experimental infection of mice and monkeys by Acanthamoeba","volume":"35","author":"Culbertson","year":"1959","journal-title":"Am. J. Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/ajcp\/46.3.305","article-title":"Hartmennella (Acanthamoeba) experimental chronic, granulomatous brain infections produced by new isolated of low virulence","volume":"46","author":"Culberston","year":"1966","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_97","first-page":"247","article-title":"Histopathological changes in the brain and lungs of mice infected with pathogenic amoebas","volume":"2\u20133","author":"Rucka","year":"1974","journal-title":"Wiad. Parazytol."},{"key":"ref_98","first-page":"103","article-title":"Histopathological changes in the brain of mice infected with the amoebas from the limax group","volume":"16","author":"Gieryng","year":"1987","journal-title":"Ann. Univ. Mariae Curie Sklodowska"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1212\/WNL.30.6.567","article-title":"Is Acanthamoeba encephalitis an opportunistic infection?","volume":"30","author":"Martinez","year":"1980","journal-title":"Neurology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1574-695X.2007.00232.x","article-title":"Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea","volume":"50","author":"Visvesvara","year":"2007","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1086\/597260","article-title":"Under the radar: Balamuthia amebic encephalitis","volume":"48","author":"Schuster","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1399-3062.2008.00335.x","article-title":"Acanthamoeba infection in a patient with chronic graft-versus-host disease occurring during treatment with voriconazole","volume":"10","author":"Kaul","year":"2008","journal-title":"Transpl. Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/j.1399-3062.2010.00535.x","article-title":"Fatal disseminated Acanthamoeba infection in a liver transplant recipient immunocompromised by combination therapies for graft-versus-host disease","volume":"12","author":"Young","year":"2010","journal-title":"Transpl. Infect. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1128\/jcm.18.6.1405-1412.1983","article-title":"Isolation of two strains of Acanthamoeba castellanii from human tissue and their pathogenicity and isoenzyme profiles","volume":"18","author":"Visvesvara","year":"1983","journal-title":"J. Clin. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1097\/00005072-198209000-00007","article-title":"Acanthamoebiasis and immunosuppression. Case report","volume":"41","author":"Martinez","year":"1982","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_106","first-page":"459","article-title":"Acanthamoeba meningoencephalitis after bone marrow transplantation","volume":"14","author":"Anderlini","year":"1994","journal-title":"Bone Marrow Transplant."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1399-3062.2003.00029.x","article-title":"Acanthamoeba castellani encephalitis following partially mismatched related donor peripheral stem cell transplantation","volume":"5","author":"Popp","year":"2003","journal-title":"Transpl. Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1001\/archderm.1995.01690230069011","article-title":"Disseminated acanthamebiasis in patients with AIDS. A report of five cases and a review of the literature","volume":"131","author":"Murakawa","year":"1995","journal-title":"Arch. Dermatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.healun.2005.09.006","article-title":"Disseminated acanthamoebiasis after lung transplantation","volume":"25","author":"Duarte","year":"2006","journal-title":"J. Heart Lung Transplant."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"108","DOI":"10.12659\/AOT.883846","article-title":"Rapidly fatal disseminated acanthamoebiasis in a single lung transplant recipient","volume":"18","author":"Afshar","year":"2013","journal-title":"Ann. Transplant."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/j.1365-4632.2006.02850.x","article-title":"Disseminated Acanthamoeba infection with sporotrichoid nodules","volume":"45","author":"Readinger","year":"2006","journal-title":"Int. J. Dermatol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3349\/ymj.1998.39.5.478","article-title":"Acanthamoebiasis in Korea: Two new cases with clinical cases review","volume":"39","author":"Im","year":"1998","journal-title":"Yonsei Med. J."},{"key":"ref_113","first-page":"346","article-title":"Disseminated acanthamoeba infection in a renal transplant recipient: A case report","volume":"50","author":"Mutreja","year":"2007","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_114","unstructured":"Gordeeva, L.M. (1978, January 19\u201326). Amoeba of limax group from the respiratory tract of man interactions with cell cultures. Proceedings of the 4th International Congress of Parasitology, Warszawa, Poland."},{"key":"ref_115","first-page":"126","article-title":"Roles of toll-like receptors: From inflammation to lung cancer progression","volume":"8","author":"Gu","year":"2018","journal-title":"Biomed. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"116671","DOI":"10.1016\/j.lfs.2019.116671","article-title":"TLRs in pulmonary diseases","volume":"233","author":"Arora","year":"2019","journal-title":"Life Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.exppara.2016.02.012","article-title":"Acanthamoeba infection in lungs of mice expressed by toll-like receptors (TLR2 and TLR4)","volume":"165","author":"Derda","year":"2016","journal-title":"Exp. Parasitol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/biof.1156","article-title":"Toll-like receptors: Role in inflammation and therapeutic potential","volume":"40","author":"Kay","year":"2014","journal-title":"Biofactors"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1084\/jem.20100734","article-title":"CD11c depletion severely disrupts Th2 induction and development in vivo","volume":"207","author":"Cook","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nri2735","article-title":"How are T(H)2-type immune responses initiated and amplified?","volume":"10","author":"Paul","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.0105-2896.2004.00191.x","article-title":"Helminth parasites: Masters of regulation","volume":"201","author":"Maizels","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Park, M.K., Cho, M.K., Kang, S.A., Park, H.K., Kim, D.H., and Yu, H.S. (2014). Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092726"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"791231","DOI":"10.1155\/2013\/791231","article-title":"Inflammatory signalings involved in airway and pulmonary diseases","volume":"2013","author":"Lee","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"639","DOI":"10.18388\/abp.2014_1825","article-title":"Cyclooxygenase pathways","volume":"61","author":"Korbecki","year":"2014","journal-title":"Acta Biochim. Pol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0223-5234(01)01197-7","article-title":"Cyclooxygenase inhibitors\u2014Current status and future prospects","volume":"36","author":"Dannhardt","year":"2001","journal-title":"Eur. J. Med. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1586\/17476348.2015.992783","article-title":"The role of prostaglandins in allergic lung inflammation and asthma","volume":"9","author":"Claar","year":"2015","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/cncr.10262","article-title":"Expression of cyclooxygenase-1 and cyclooxygenase-2 in bronchial epithelium and nonsmall cell lung carcinoma","volume":"94","author":"Hasturk","year":"2002","journal-title":"Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1177\/0192623308329474","article-title":"Pathophysiology of cyclooxygenase inhibition in animal models","volume":"37","author":"Radi","year":"2009","journal-title":"Toxicol. Pathol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1183\/09031936.00186911","article-title":"Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue","volume":"40","author":"Szymanski","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.exppara.2016.07.009","article-title":"The inflammatory effect of infection with Hymenolepis diminuta via the increased expression and activity of COX-1 and COX-2 in the rat jejunum and colon","volume":"169","author":"Gutowska","year":"2016","journal-title":"Exp. Parasitol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"\u0141anocha-Arendarczyk, N., Baranowska-Bosiacka, I., Kot, K., Gutowska, I., Kolasa-Wo\u0142osiuk, A., Chlubek, D., and Kosik-Bogacka, D. (2018). Expression and Activity of COX-1 and COX-2 in Acanthamoeba sp.-Infected Lungs According to the Host Immunological Status. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010121"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative stress and antioxidant defense","volume":"5","author":"Birben","year":"2012","journal-title":"World Allergy Organ. J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1165\/rcmb.2008-0330OC","article-title":"Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes","volume":"41","author":"Hosakote","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00436-005-1377-8","article-title":"Antioxidant potential of rat liver in experimental infection with Fasciola hepatica","volume":"96","author":"Kolodziejczyk","year":"2005","journal-title":"Parasitol. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1007\/s00436-012-3006-7","article-title":"Functional expression and characterization of an iron-containing superoxide dismutase of Acanthamoeba castellanii","volume":"111","author":"Kim","year":"2012","journal-title":"Parasitol. Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1007\/s00436-018-5992-6","article-title":"Effect of oxidative stress on vital indicators of Acanthamoeba castellanii (T4 genotype)","volume":"117","author":"Motavalli","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_137","first-page":"197","article-title":"Proteolytic enzymes of pathogenic and non-pathogenic strains of Acanthamoeba spp.","volume":"44","author":"Hadas","year":"1993","journal-title":"Trop. Med. Parasitol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.exppara.2015.09.005","article-title":"Juglone induces cell death of Acanthamoeba through increased production of reactive oxygen species","volume":"159","author":"Jha","year":"2015","journal-title":"Exp. Parasitol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.exppara.2018.09.002","article-title":"Relationship between antioxidant defense in Acanthamoeba spp. infected lungs and host immunological status","volume":"193","author":"Gutowska","year":"2018","journal-title":"Exp. Parasitol."},{"key":"ref_140","first-page":"367","article-title":"Histological changes in the lungs of mice experimentally infected with amoebas from the limax group. Histopathological changes in the lungs","volume":"39","author":"Gieryng","year":"1993","journal-title":"Wiad. Parazytol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Elsheikha, H.M., Siddiqui, R., and Khan, N.A. (2020). Drug Discovery against Acanthamoeba Infections: Present Knowledge and Unmet Needs. Pathogens, 9.","DOI":"10.3390\/pathogens9050405"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1086\/589747","article-title":"Infectious Diseases Society of America. The management of encephalitis: Clinical practice guidelines by the Infectious Diseases Society of America","volume":"47","author":"Tunkel","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_143","unstructured":"Centers for Disease Control and Prevention (CDC) (2013). Investigational drug available directly from CDC for the treatment of infections with free-living amebae. MMWR Morb. Mortal. Wkly. Rep., 62, 666."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1261\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:16:17Z","timestamp":1760159777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,27]]},"references-count":143,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22031261"],"URL":"https:\/\/doi.org\/10.3390\/ijms22031261","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,27]]}}}