{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:46:24Z","timestamp":1780641984877,"version":"3.54.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Cryptococcus neoformans<\/jats:italic>\n is a fungus that poses a significant threat to human health, with its polysaccharide capsule being a key virulence factor that can upregulate the expression of host gene\n ARG1<\/jats:italic>\n , encoding arginase-1, which suppresses T-cell-mediated antifungal immune responses. Nanoplastics may cause oxidative and mitochondrial stress in mammalian cells, potentially impacting fungal physiology and pathogenic mechanisms as well.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We utilized mouse models and fungal burden assays to investigate the effects of polystyrene nanoparticles (PS-NPs) on\n C. neoformans<\/jats:italic>\n infection. Mice were subjected to oropharyngeal aspiration of 50 \u03bcl of 80 nm PS-NPs at a concentration of 5 \u03bcg\/\u03bcl, administered three times a week over a specified duration. To assess the impact of PS-NPs on\n C. neoformans<\/jats:italic>\n mitochondria, we measured intracellular reactive oxygen species (ROS) levels, mitochondrial superoxide, mitochondrial membrane potential, and intracellular ATP levels in whole fungal cells. Additionally, we performed RNA-Seq analysis and metabolomics studies to evaluate the effects of PS-NPs at a concentration of 0.3 \u03bcg\/\u03bcL on the RNA and metabolic profiles of\n C. neoformans<\/jats:italic>\n mitochondria.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our study demonstrated that PS-NPs significantly prolonged the survival of mice infected with\n C. neoformans<\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0=\u00a00.0058). PS-NPs exposure resulted in a 30% reduction in\n ARG1<\/jats:italic>\n mRNA expression and enhanced T-cell-mediated antifungal immunity. Additionally, PS-NPs inhibited fungal capsule formation by approximately 40% in infected mice and 70% in capsule induction medium. Given the close link between the mitochondria of\n C. neoformans<\/jats:italic>\n and capsule formation, we further investigated the effects of PS-NPs on mitochondrial function. Exposure to PS-NPs led to mitochondrial dysfunction in\n C. neoformans<\/jats:italic>\n , as evidenced by a threefold increase in ROS, a 1.7-fold increase in mitochondrial membrane potential, and disruptions in mitochondrial transcription and metabolism.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These results suggest that PS-NPs inhibit the formation of the\n C. neoformans<\/jats:italic>\n capsule, potentially by inducing mitochondrial dysfunction. Furthermore, the findings highlight the broader implications of PS-NPs on fungal virulence and the dynamics of host-pathogen interactions, underscoring their significance in advancing our understanding of these complex relationships.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1708192","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:24:59Z","timestamp":1762323899000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Polystyrene nanoparticles reduce the Cryptococcus neoformans virulence via induction of mitochondrial dysfunction"],"prefix":"10.3389","volume":"15","author":[{"given":"Dongnan","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Bu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3534","DOI":"10.1038\/s41596-023-00886-9","article-title":"Exposure protocol for ecotoxicity testing of microplastics and nanoplastics","volume":"18","author":"Abdolahpur Monikh","year":"2023","journal-title":"Nat. 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