{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:38:40Z","timestamp":1779363520441,"version":"3.53.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010941","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI145559"],"award-info":[{"award-number":["R01AI145559"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019274","name":"National Institute of Mental Health and Neurosciences","doi-asserted-by":"publisher","award":["MH096625"],"award-info":[{"award-number":["MH096625"]}],"id":[{"id":"10.13039\/100019274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019274","name":"National Institute of Mental Health and Neurosciences","doi-asserted-by":"publisher","award":["MH128082"],"award-info":[{"award-number":["MH128082"]}],"id":[{"id":"10.13039\/100019274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS105584"],"award-info":[{"award-number":["NS105584"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The University of Texas Medical Branch internal funding"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The encapsulated fungus <jats:italic>Cryptococcus neoformans<\/jats:italic> is the most common cause of fungal meningitis, with the highest rate of disease in patients with AIDS or immunosuppression. This microbe enters the human body via inhalation of infectious particles. <jats:italic>C<\/jats:italic>. <jats:italic>neoformans<\/jats:italic> capsular polysaccharide, in which the major component is glucuronoxylomannan (GXM), extensively accumulates in tissues and compromises host immune responses. <jats:italic>C<\/jats:italic>. <jats:italic>neoformans<\/jats:italic> travels from the lungs to the bloodstream and crosses to the brain via transcytosis, paracytosis, or inside of phagocytes using a \u201cTrojan horse\u201d mechanism. The fungus causes life-threatening meningoencephalitis with high mortality rates. Hence, we investigated the impact of intranasal exogenous GXM administration on <jats:italic>C<\/jats:italic>. <jats:italic>neoformans<\/jats:italic> infection in C57BL\/6 mice. GXM enhances cryptococcal pulmonary infection and facilitates fungal systemic dissemination and brain invasion. Pre-challenge of GXM results in detection of the polysaccharide in lungs, serum, and surprisingly brain, the latter likely reached through the nasal cavity. GXM significantly alters endothelial cell tight junction protein expression <jats:italic>in vivo<\/jats:italic>, suggesting significant implications for the <jats:italic>C<\/jats:italic>. <jats:italic>neoformans<\/jats:italic> mechanisms of brain invasion. Using a microtiter transwell system, we showed that GXM disrupts the trans-endothelial electrical resistance, weakening human brain endothelial cell monolayers co-cultured with pericytes, supportive cells of blood vessels\/capillaries found in the blood-brain barrier (BBB) to promote <jats:italic>C<\/jats:italic>. <jats:italic>neoformans<\/jats:italic> BBB penetration. Our findings should be considered in the development of therapeutics to combat the devastating complications of cryptococcosis that results in an estimated ~200,000 deaths worldwide each year.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010941","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T17:32:46Z","timestamp":1682703166000},"page":"e1010941","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Glucuronoxylomannan intranasal challenge prior to Cryptococcus neoformans pulmonary infection enhances cerebral cryptococcosis in rodents"],"prefix":"10.1371","volume":"19","author":[{"given":"Hiu Ham","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan J.","family":"Carmichael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"R\u00edbeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana N.","family":"Parisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"Munzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L.","family":"Charles-Ni\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed F.","family":"Hamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ettiman","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayush","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiya","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikki B.","family":"Rooklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Sher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Carrillo-Sepulveda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliseo A.","family":"Eugenin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Dores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-6501","authenticated-orcid":true,"given":"Luis R.","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"issue":"8","key":"ppat.1010941.ref001","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis","volume":"17","author":"R Rajasingham","year":"2017","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"ppat.1010941.ref002","doi-asserted-by":"crossref","first-page":"E66","DOI":"10.1542\/peds.107.5.e66","article-title":"Serologic evidence for Cryptococcus neoformans infection in early childhood","volume":"107","author":"DL Goldman","year":"2001","journal-title":"Pediatrics"},{"issue":"6","key":"ppat.1010941.ref003","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/clinids\/13.6.1163","article-title":"The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis","volume":"13","author":"SM Levitz","year":"1991","journal-title":"Rev Infect Dis"},{"issue":"3","key":"ppat.1010941.ref004","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1128\/iai.17.3.634-638.1977","article-title":"Cryptococcus neoformans: size range of infectious particles from aerosolized soil","volume":"17","author":"JB Neilson","year":"1977","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1010941.ref005","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1371\/journal.pmed.0040021","article-title":"Determinants of disease presentation and outcome during cryptococcosis: the CryptoA\/D study.","volume":"4","author":"F Dromer","year":"2007","journal-title":"PLoS Med."},{"issue":"12","key":"ppat.1010941.ref006","doi-asserted-by":"crossref","first-page":"6314","DOI":"10.1128\/IAI.67.12.6314-6320.1999","article-title":"Cytokine profiles of AIDS patients are similar to those of mice with disseminated Cryptococcus neoformans infection","volume":"67","author":"O Lortholary","year":"1999","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1010941.ref007","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1086\/341564","article-title":"Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia","volume":"186","author":"F Chretien","year":"2002","journal-title":"J Infect Dis"},{"issue":"9","key":"ppat.1010941.ref008","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1128\/IAI.72.9.4985-4995.2004","article-title":"Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier","volume":"72","author":"YC Chang","year":"2004","journal-title":"Infect Immun"},{"issue":"7","key":"ppat.1010941.ref009","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.2164-0947.1958.tb00625.x","article-title":"Capsule synthesis by Cryptococcus neoformans","volume":"20","author":"ML Littman","year":"1958","journal-title":"Trans N Y Acad Sci"},{"key":"ppat.1010941.ref010","doi-asserted-by":"crossref","first-page":"773","DOI":"10.3181\/00379727-101-25090","article-title":"Effect of degree of encapsulation upon virulence of Cryptococcus neoformans","volume":"101","author":"ML Littman","year":"1959","journal-title":"Proc Soc Exp Biol Med"},{"issue":"1","key":"ppat.1010941.ref011","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1128\/iai.20.1.262-266.1978","article-title":"Cryptococcus neoformans: pseudohyphal forms surviving culture with Acanthamoeba polyphaga","volume":"20","author":"JB Neilson","year":"1978","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1010941.ref012","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/BF00636177","article-title":"Decreased virulence in stable, acapsular mutants of cryptococcus neoformans","volume":"79","author":"RA Fromtling","year":"1982","journal-title":"Mycopathologia"},{"issue":"5","key":"ppat.1010941.ref013","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1128\/iai.62.5.1507-1512.1994","article-title":"Polysaccharide antigens of the capsule of Cryptococcus neoformans","volume":"62","author":"R Cherniak","year":"1994","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1010941.ref014","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1128\/iai.63.9.3448-3453.1995","article-title":"Tissue localization of Cryptococcus neoformans glucuronoxylomannan in the presence and absence of specific antibody","volume":"63","author":"DL Goldman","year":"1995","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1010941.ref015","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/mmy.38.6.407.417","article-title":"Immunoregulation by capsular components of Cryptococcus neoformans","volume":"38","author":"A. Vecchiarelli","year":"2000","journal-title":"Med Mycol"},{"issue":"9","key":"ppat.1010941.ref016","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1089\/aid.1994.10.1079","article-title":"Enhancement of HIV type 1 infectivity in vitro by capsular polysaccharide of Cryptococcus neoformans and Haemophilus influenzae","volume":"10","author":"M Pettoello-Mantovani","year":"1994","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"1","key":"ppat.1010941.ref017","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1093\/clinids\/23.1.194","article-title":"Polysaccharide antigen in brain tissue of AIDS patients with cryptococcal meningitis","volume":"23","author":"SC Lee","year":"1996","journal-title":"Clin Infect Dis"},{"issue":"13","key":"ppat.1010941.ref018","doi-asserted-by":"crossref","first-page":"10423","DOI":"10.1074\/jbc.M007136200","article-title":"Regulation of tight junction permeability and occludin phosphorylation by Rhoa-p160ROCK-dependent and -independent mechanisms","volume":"276","author":"T Hirase","year":"2001","journal-title":"J Biol Chem"},{"key":"ppat.1010941.ref019","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1742-2094-8-28","article-title":"Protein kinase C-alpha signals P115RhoGEF phosphorylation and RhoA activation in TNF-alpha-induced mouse brain microvascular endothelial cell barrier dysfunction","volume":"8","author":"J Peng","year":"2011","journal-title":"J Neuroinflammation"},{"issue":"4","key":"ppat.1010941.ref020","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1007\/s11481-021-10029-0","article-title":"SARS-CoV-2 Spike Protein Disrupts Blood-Brain Barrier Integrity via RhoA Activation.","volume":"16","author":"BJ DeOre","year":"2021","journal-title":"J Neuroimmune Pharmacol."},{"issue":"3","key":"ppat.1010941.ref021","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1128\/iai.18.3.701-707.1977","article-title":"Immune response to Cryptococcus neoformans soluble polysaccharide: immunological unresponsiveness","volume":"18","author":"TR Kozel","year":"1977","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1010941.ref022","first-page":"1309","article-title":"Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system","volume":"136","author":"RA Sobel","year":"1990","journal-title":"Am J Pathol"},{"key":"ppat.1010941.ref023","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1146\/annurev.neuro.22.1.11","article-title":"The cell biology of the blood-brain barrier","volume":"22","author":"LL Rubin","year":"1999","journal-title":"Annu Rev Neurosci"},{"issue":"7","key":"ppat.1010941.ref024","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/S0962-8924(99)01578-0","article-title":"Occludin and claudins in tight-junction strands: leading or supporting players","volume":"9","author":"S Tsukita","year":"1999","journal-title":"Trends Cell Biol"},{"issue":"3","key":"ppat.1010941.ref025","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1128\/iai.62.3.1079-1088.1994","article-title":"Monoclonal antibodies to Cryptococcus neoformans capsular polysaccharide modify the course of intravenous infection in mice","volume":"62","author":"S Mukherjee","year":"1994","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1010941.ref026","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1128\/IAI.00094-07","article-title":"The relative susceptibility of mouse strains to pulmonary Cryptococcus neoformans infection is associated with pleiotropic differences in the immune response","volume":"75","author":"O Zaragoza","year":"2007","journal-title":"Infect Immun"},{"issue":"26","key":"ppat.1010941.ref027","doi-asserted-by":"crossref","first-page":"15191","DOI":"10.1073\/pnas.261452898","article-title":"The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction","volume":"98","author":"CJ Cohen","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"43","key":"ppat.1010941.ref028","doi-asserted-by":"crossref","first-page":"36147","DOI":"10.1074\/jbc.M112.389676","article-title":"Cryptococcus neoformans activates RhoGTPase proteins followed by protein kinase C, focal adhesion kinase, and ezrin to promote traversal across the blood-brain barrier","volume":"287","author":"JC Kim","year":"2012","journal-title":"J Biol Chem"},{"issue":"3","key":"ppat.1010941.ref029","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1113\/jphysiol.2014.283853","article-title":"In vivo roles for myosin phosphatase targeting subunit-1 phosphorylation sites T694 and T852 in bladder smooth muscle contraction","volume":"593","author":"CP Chen","year":"2015","journal-title":"J Physiol"},{"issue":"2","key":"ppat.1010941.ref030","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/jcp.22347","article-title":"Thrombin promotes actin stress fiber formation in RPE through Rho\/ROCK-mediated MLC phosphorylation","volume":"226","author":"AY Ruiz-Loredo","year":"2011","journal-title":"J Cell Physiol"},{"issue":"1","key":"ppat.1010941.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-011-0847-6","article-title":"Brain microvascular pericytes in health and disease","volume":"122","author":"T Dalkara","year":"2011","journal-title":"Acta Neuropathol"},{"issue":"1","key":"ppat.1010941.ref032","doi-asserted-by":"crossref","first-page":"e0011068","DOI":"10.1371\/journal.pntd.0011068","article-title":"Clinical and pathological characterization of Central Nervous System cryptococcosis in an experimental mouse model of stereotaxic intracerebral infection.","volume":"17","author":"MF Hamed","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"ppat.1010941.ref033","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/BF01641291","article-title":"The course of cryptococcal capsular polysaccharide antigenemia\/human cryptococcal polysaccharide elimination kinetics.","volume":"11","author":"R Eng","year":"1983","journal-title":"Infection"},{"issue":"6","key":"ppat.1010941.ref034","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1086\/515329","article-title":"Effect of immune mechanisms on the pharmacokinetics and organ distribution of cryptococcal polysaccharide","volume":"177","author":"N Lendvai","year":"1998","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1010941.ref035","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF00436580","article-title":"Cryptococcal capsular polysaccharide clearance in nonimmune mice","volume":"78","author":"HG Muchmore","year":"1982","journal-title":"Mycopathologia"},{"issue":"3","key":"ppat.1010941.ref036","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1574-695X.1997.tb01089.x","article-title":"The in vitro interaction of Cryptococcus neoformans with human lung epithelial cells","volume":"19","author":"GJ Merkel","year":"1997","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"4","key":"ppat.1010941.ref037","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.micinf.2005.10.018","article-title":"Phospholipase B activity enhances adhesion of Cryptococcus neoformans to a human lung epithelial cell line","volume":"8","author":"R Ganendren","year":"2006","journal-title":"Microbes Infect"},{"key":"ppat.1010941.ref038","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fcimb.2014.00106","article-title":"Mannoprotein MP84 mediates the adhesion of Cryptococcus neoformans to epithelial lung cells","volume":"4","author":"PA Teixeira","year":"2014","journal-title":"Front Cell Infect Microbiol"},{"key":"ppat.1010941.ref039","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.fgb.2013.08.005","article-title":"The heat shock protein (Hsp) 70 of Cryptococcus neoformans is associated with the fungal cell surface and influences the interaction between yeast and host cells.","volume":"60","author":"CP Silveira","year":"2013","journal-title":"Fungal Genet Biol"},{"issue":"10","key":"ppat.1010941.ref040","doi-asserted-by":"crossref","first-page":"6350","DOI":"10.1128\/IAI.73.10.6350-6362.2005","article-title":"Specific antibody can prevent fungal biofilm formation and this effect correlates with protective efficacy","volume":"73","author":"LR Martinez","year":"2005","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1010941.ref041","article-title":"Cryptococcus-Epithelial Interactions.","volume":"3","author":"LM Taylor-Smith","year":"2017","journal-title":"J Fungi (Basel)."},{"issue":"27","key":"ppat.1010941.ref042","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1016\/j.vaccine.2009.03.089","article-title":"The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies","volume":"27","author":"A Nakouzi","year":"2009","journal-title":"Vaccine"},{"issue":"1","key":"ppat.1010941.ref043","doi-asserted-by":"crossref","first-page":"21110","DOI":"10.1038\/s41598-021-00708-6","article-title":"Deficiency of lung-specific claudin-18 leads to aggravated infection with Cryptococcus deneoformans through dysregulation of the microenvironment in lungs.","volume":"11","author":"K Sato","year":"2021","journal-title":"Sci Rep."},{"issue":"9","key":"ppat.1010941.ref044","doi-asserted-by":"crossref","first-page":"4762","DOI":"10.1128\/IAI.70.9.4762-4771.2002","article-title":"Cryptococcal glucuronoxylomannan inhibits adhesion of neutrophils to stimulated endothelium in vitro by affecting both neutrophils and endothelial cells","volume":"70","author":"PM Ellerbroek","year":"2002","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1010941.ref045","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1462-5822.2004.00384.x","article-title":"Cryptococcal glucuronoxylomannan interferes with neutrophil rolling on the endothelium","volume":"6","author":"PM Ellerbroek","year":"2004","journal-title":"Cell Microbiol"},{"issue":"4","key":"ppat.1010941.ref046","doi-asserted-by":"crossref","first-page":"e1010389","DOI":"10.1371\/journal.ppat.1010389","article-title":"Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection","volume":"18","author":"JF Gibson","year":"2022","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1010941.ref047","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s12038-014-9496-y","article-title":"Lack of IL-6 increases blood-brain barrier permeability in fungal meningitis","volume":"40","author":"X Li","year":"2015","journal-title":"J Biosci"},{"issue":"5","key":"ppat.1010941.ref048","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/S0002-9440(10)63734-0","article-title":"Urease expression by Cryptococcus neoformans promotes microvascular sequestration, thereby enhancing central nervous system invasion","volume":"164","author":"MA Olszewski","year":"2004","journal-title":"Am J Pathol"},{"issue":"10","key":"ppat.1010941.ref049","doi-asserted-by":"crossref","first-page":"5755","DOI":"10.4049\/jimmunol.0901638","article-title":"The absence of serum IgM enhances the susceptibility of mice to pulmonary challenge with Cryptococcus neoformans","volume":"184","author":"KS Subramaniam","year":"2010","journal-title":"J Immunol"},{"key":"ppat.1010941.ref050","doi-asserted-by":"crossref","first-page":"916","DOI":"10.4049\/jimmunol.94.6.916","article-title":"Cryptococcus Neoformans Polysaccharide: Studies of Serologic Properties and Role in Infection","volume":"94","author":"JE Bennett","year":"1965","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1010941.ref051","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00483-19","article-title":"Intranasal Inoculation of Cryptococcus neoformans in Mice Produces Nasal Infection with Rapid Brain Dissemination","volume":"4","author":"C Coelho","year":"2019","journal-title":"mSphere"},{"issue":"12","key":"ppat.1010941.ref052","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1007\/s10072-013-1461-2","article-title":"Pseudo-subarachnoid hemorrhage in cryptococcal meningitis: MRI findings and pathological study.","volume":"34","author":"Y Nakae","year":"2013","journal-title":"Neurol Sci"},{"issue":"1","key":"ppat.1010941.ref053","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12883-017-0934-y","article-title":"Subarachnoid small vein occlusion due to inflammatory fibrosis-a possible mechanism for cerebellar infarction in cryptococcal meningoencephalitis: a case report.","volume":"17","author":"Y Shimoda","year":"2017","journal-title":"BMC Neurol."},{"issue":"5","key":"ppat.1010941.ref054","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/infdis\/jix033","article-title":"Differences in Immunologic Factors Among Patients Presenting with Altered Mental Status During Cryptococcal Meningitis","volume":"215","author":"S Lofgren","year":"2017","journal-title":"J Infect Dis"},{"issue":"23","key":"ppat.1010941.ref055","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1097\/CM9.0000000000001191","article-title":"Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis: a 2-year retrospective analysis","volume":"133","author":"W Song","year":"2020","journal-title":"Chin Med J (Engl)."},{"issue":"Pt 11","key":"ppat.1010941.ref056","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1099\/jmm.0.05230-0","article-title":"Cryptococcus neoformans induces alterations in the cytoskeleton of human brain microvascular endothelial cells","volume":"52","author":"SHM Chen","year":"2003","journal-title":"J Med Microbiol"},{"issue":"10","key":"ppat.1010941.ref057","doi-asserted-by":"crossref","first-page":"3408","DOI":"10.1182\/blood.V93.10.3408.410k37_3408_3417","article-title":"Agonist-induced regulation of myosin phosphatase activity in human platelets through activation of Rho-kinase","volume":"93","author":"Y Suzuki","year":"1999","journal-title":"Blood"},{"issue":"1","key":"ppat.1010941.ref058","doi-asserted-by":"crossref","first-page":"C195","DOI":"10.1152\/ajpcell.2000.279.1.C195","article-title":"ROCK mediates thrombin\u2019s endothelial barrier dysfunction","volume":"279","author":"JM Carbajal","year":"2000","journal-title":"Am J Physiol Cell Physiol"},{"issue":"4","key":"ppat.1010941.ref059","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/infdis\/jit117","article-title":"Methamphetamine alters blood brain barrier protein expression in mice, facilitating central nervous system infection by neurotropic Cryptococcus neoformans","volume":"208","author":"EA Eugenin","year":"2013","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1010941.ref060","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02183-16","article-title":"Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen.","volume":"8","author":"FH Santiago-Tirado","year":"2017","journal-title":"mBio."},{"issue":"9","key":"ppat.1010941.ref061","doi-asserted-by":"crossref","first-page":"e45083","DOI":"10.1371\/journal.pone.0045083","article-title":"Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.","volume":"7","author":"HK Tseng","year":"2012","journal-title":"PLoS One."},{"issue":"3","key":"ppat.1010941.ref062","first-page":"e01101","article-title":"Invasion of the central nervous system by Cryptococcus neoformans requires a secreted fungal metalloprotease.","volume":"5","author":"K Vu","year":"2014","journal-title":"mBio."},{"issue":"11","key":"ppat.1010941.ref063","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1128\/EC.00240-09","article-title":"Immortalized human brain endothelial cell line HCMEC\/D3 as a model of the blood-brain barrier facilitates in vitro studies of central nervous system infection by Cryptococcus neoformans","volume":"8","author":"K Vu","year":"2009","journal-title":"Eukaryot Cell"},{"issue":"7323","key":"ppat.1010941.ref064","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature09522","article-title":"Pericytes regulate the blood-brain barrier","volume":"468","author":"A Armulik","year":"2010","journal-title":"Nature"},{"key":"ppat.1010941.ref065","doi-asserted-by":"crossref","first-page":"e0431522","DOI":"10.1128\/spectrum.04315-22","article-title":"Roles for Microglia in Cryptococcal Brain Dissemination in the Zebrafish Larva.","volume":"2023","author":"JA Nielson","year":"2023","journal-title":"Microbiol Spectr"},{"issue":"6","key":"ppat.1010941.ref066","doi-asserted-by":"crossref","first-page":"e1000412","DOI":"10.1371\/journal.pbio.1000412","article-title":"Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research","volume":"8","author":"C Kilkenny","year":"2010","journal-title":"PLoS Biol"},{"issue":"2","key":"ppat.1010941.ref067","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1128\/EC.3.2.385-392.2004","article-title":"Cryptococcus neoformans CAP59 (or Cap59p) is involved in the extracellular trafficking of capsular glucuronoxylomannan.","volume":"3","author":"J Garcia-Rivera","year":"2004","journal-title":"Eukaryot Cell"},{"issue":"8","key":"ppat.1010941.ref068","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1128\/EC.00122-07","article-title":"Self-aggregation of Cryptococcus neoformans capsular glucuronoxylomannan is dependent on divalent cations","volume":"6","author":"L Nimrichter","year":"2007","journal-title":"Eukaryot Cell"},{"issue":"1","key":"ppat.1010941.ref069","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0022-1759(92)90209-C","article-title":"Monoclonal antibody based ELISAs for cryptococcal polysaccharide","volume":"154","author":"A Casadevall","year":"1992","journal-title":"J Immunol Methods"},{"issue":"2","key":"ppat.1010941.ref070","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0021-9258(17)41083-0","article-title":"A specific color reaction for glucuronic acid","volume":"171","author":"Z. Dische","year":"1947","journal-title":"J Biol Chem"},{"issue":"4265","key":"ppat.1010941.ref071","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/168167a0","article-title":"A colorimetric method for the determination of sugars","volume":"168","author":"M Dubois","year":"1951","journal-title":"Nature"},{"issue":"6","key":"ppat.1010941.ref072","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1128\/IAI.72.6.3674-3679.2004","article-title":"Antibody to Cryptococcus neoformans glucuronoxylomannan inhibits the release of capsular antigen","volume":"72","author":"LR Martinez","year":"2004","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1010941.ref073","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.biomaterials.2009.09.087","article-title":"The use of chitosan to damage Cryptococcus neoformans biofilms.","volume":"31","author":"LR Martinez","year":"2010","journal-title":"Biomaterials"},{"issue":"4","key":"ppat.1010941.ref074","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/jnc.13603","article-title":"Methamphetamine compromises gap junctional communication in astrocytes and neurons","volume":"137","author":"P Castellano","year":"2016","journal-title":"J Neurochem"},{"issue":"1","key":"ppat.1010941.ref075","doi-asserted-by":"crossref","first-page":"8207","DOI":"10.1038\/s41598-021-87728-4","article-title":"Methamphetamine facilitates pulmonary and splenic tissue injury and reduces T cell infiltration in C57BL\/6 mice after antigenic challenge.","volume":"11","author":"AC Hernandez-Santini","year":"2021","journal-title":"Sci Rep."},{"issue":"9","key":"ppat.1010941.ref076","first-page":"e2273","article-title":"In vitro Assays for Measuring Endothelial Permeability byTranswells and Electrical Impedance Systems.","volume":"7","author":"HR Chen","year":"2017","journal-title":"Bio Protoc."},{"issue":"4","key":"ppat.1010941.ref077","doi-asserted-by":"crossref","first-page":"e61982","DOI":"10.1371\/journal.pone.0061982","article-title":"Emerging role of angiotensin type 2 receptor (AT2R)\/Akt\/NO pathway in vascular smooth muscle cell in the hyperthyroidism.","volume":"8","author":"MA Carrillo-Sepulveda","year":"2013","journal-title":"PLoS One."}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010941","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010941","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T18:59:39Z","timestamp":1683745179000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010941"}},"subtitle":[],"editor":[{"given":"Maurizio","family":"Del Poeta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":77,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010941","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1010941","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]}}}