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Due to the high frequency of multidrug-resistant strains and mortality rate, C. auris is considered a critical health threat by the Centers for Disease Control and Prevention and the World Health Organization. Like other pathogens, C. auris employs virulence factors that are delivered by extracellular vesicles (EVs). We have shown that EVs from C. auris (CauEVs) activate murine phagocytes, boosting innate immune mechanisms. However, the effect of fungal EVs on lymphoid cells has not yet been addressed. Upon activation, CD4 T cells undergo clonal expansion and cytokine production that orchestrate immune responses to eradicate invading pathogens, a process of critical importance in controlling invasive candidiasis. Here, we show that the treatment with CauEVs inhibited the activation-induced CD4 T cells proliferation in a dose-dependent manner. Notably, we found that CauEVs acted at early events downstream to the T cell receptor signaling, inhibiting the MAPK phosphorylation. Interestingly, the inhibition of CD4 T cell proliferation by CauEVs was associated with an inhibition of the IL-2 signaling, followed by an increase on the IL-2 production that failed to restore proliferation. Taken together, our results suggest that CauEVs may contain an immunomodulatory factor(s) that affect the CD4 T cell activation and their fate from early to later events in a previously undescribed mechanism.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf302","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T14:07:46Z","timestamp":1765030066000},"source":"Crossref","is-referenced-by-count":2,"title":["Extracellular vesicles from\n                    <i>Candidozyma<\/i>\n                    (\n                    <i>Candida<\/i>\n                    )\n                    <i>auris<\/i>\n                    inhibit proliferation of CD4 T cells by disrupting the IL-2 axis"],"prefix":"10.1093","volume":"215","author":[{"given":"Yair","family":"Botbol","sequence":"first","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine , Bronx, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius","family":"Alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biof\u00edsica de Fungos, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Nimrichter","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro , Rio de Janeiro,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Macian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine , Bronx, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D","family":"Nosanchuk","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine , Bronx, NY,","place":["United States"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , Bronx, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-2432","authenticated-orcid":false,"given":"Daniel","family":"Zamith-Miranda","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine , Bronx, NY,","place":["United States"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , Bronx, NY,","place":["United 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