{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:12:01Z","timestamp":1771920721415,"version":"3.50.1"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019305","name":"Manipal Academy of Higher Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019305","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                      causes lethal meningoencephalitis and long-term neurological deficits, particularly in immunocompromised hosts of any age group. After penetrating the airway and crossing the blood-tissue barriers,\n                      <jats:italic>C. neoformans<\/jats:italic>\n                      rapidly enters the brain, where it extensively releases the capsular polysaccharide glucuronoxylomannan (GXM), a major virulence factor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Cryptococcus neoformans (<\/jats:italic>\n                      ATCC 32045) was used to isolate and purify GXM. This study utilized human-induced pluripotent stem cell-derived 2D cultured neural stem cells, neurons, and microglia-deficient cerebral organoids to identify GXM-induced pathogenesis. Cryosectioning of frozen tissues, immunostaining, western blot analysis and untargeted lipidomics were employed to identify the GXM-induced impact on cellular proliferation and cell death, as well as possible cellular and molecular targets. The study utilized the first-ever atomistic models of neuronal and neural stem cells (NSC) membranes, built using a proportion of the original lipid compositions using the Materials Science Suite to identify subtle interactions between the membranes and GXM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GXM exposure induced subtle cell death, but progenitor cell proliferation was unaffected. Interestingly, GXM preferentially targeted neurons irrespective of the abundance of NSCs and astrocytes. Synaptophysin, an integral component of neuronal synaptic vesicles, was significantly reduced following GXM exposure. The untargeted lipidomics analysis revealed higher phosphatidylcholine levels and reduced phosphatidylethanolamine levels in human neurons compared to other cell types. The atomistic models revealed a significant attractive interaction energy between GXM and neuronal membranes, with phosphatidylcholine being primarily responsible.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study provides novel evidence that lipid membranes containing higher phosphatidylcholine are a primary target of GXM of\n                      <jats:italic>C. neoformans<\/jats:italic>\n                      and could be the possible reason for the preferential targeting of GXM to neurons. Additionally, GXM induced synaptic deficits in neurons, which could be a significant factor contributing to the neurological dysfunctions observed in this fungal infection. This study opens the mechanism of pathogenesis and targeting opportunities for treating\n                      <jats:italic>C. neoformans-<\/jats:italic>\n                      induced meningoencephalitis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1687068","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:18:57Z","timestamp":1767676737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Host-membrane lipid composition controls Cryptococcus neoformans cellular targets"],"prefix":"10.3389","volume":"16","author":[{"given":"Aswathi I.","family":"Ramesh","sequence":"first","affiliation":[{"name":"Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumukha","family":"Hegde","sequence":"additional","affiliation":[{"name":"Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aarsh Mahendra","family":"Dabhi","sequence":"additional","affiliation":[{"name":"Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sriram","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Schrodinger India Private Limited","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Chandran","sequence":"additional","affiliation":[{"name":"Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivakumar K.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prakash Peralam","family":"Yegneswaran","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavitha","family":"Saravu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Kasturba Medical College Manipal, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.V.","family":"Mallikarjuna","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Manipal College of Health Professions, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavitha S.","family":"Shettigar","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Manipal College of Health Professions, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pritesh","family":"Bhat","sequence":"additional","affiliation":[{"name":"Schrodinger India Private Limited","place":["Bengaluru, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varadaraj","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.R.","family":"Sabitha","sequence":"additional","affiliation":[{"name":"Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education","place":["Manipal, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indumathi","family":"Mariappan","sequence":"additional","affiliation":[{"name":"Center for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Center (BHERC), L.V. 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