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Hyphal invasion induces apoptosis of renal tubular epithelial cells (RTEC), a key driver of kidney pathology, yet intrinsic renal protective mechanisms remain poorly defined. We identify fibrinolytic tissue-type plasminogen activator (tPA) as a critical mediator of renal tissue protection in candidiasis. tPA is induced by IL-17 and TNF\u03b1 in renal endothelial cells and RTEC. tPA signals through low-density lipoprotein receptor\u2013related protein 1 (LRP1) and activates ERK1\/2 signaling to suppress apoptosis in RTEC. Mice with RTEC-specific deletion of LRP1 exhibited exaggerated kidney damage during candidiasis. Administration of a nonenzymatic form of tPA recapitulated the protective effect of tPA by limiting RTEC apoptosis. These findings reveal the role of tPA\/LRP1 axis in preserving renal integrity in candidiasis and suggest clinically approved tPA as a potential therapeutic strategy to mitigate candidiasis-associated tissue injury.<\/jats:p>","DOI":"10.1084\/jem.20260530","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:20:47Z","timestamp":1783578047000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Tissue-type plasminogen activator protects against kidney damage in invasive fungal infection"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0864-6642","authenticated-orcid":true,"given":"Wonseok","family":"Choi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pittsburgh 1 Division of Rheumatology and Clinical Immunology, Department of Medicine, , 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