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Fungi","JoF"],"abstract":"<jats:p>Fungal infections remain a major global health challenge, underscoring the need to better understand host\u2013pathogen interactions. Extracellular vesicles (EVs) released by fungal pathogens are emerging as key modulators of immune responses. Here, we investigated how EVs from Candida albicans and Aspergillus fumigatus influence macrophage activation, focusing on the integration of pattern recognition receptors (PRRs) and cytosolic sensing pathways. EVs were characterized by nanoparticle tracking analysis, zeta potential, and cryo-electron microscopy. Human THP-1-derived macrophages were stimulated with fungal EVs, and cytokine production, gene expression, and signaling pathway activation were assessed by ELISA, RT-qPCR, and Western blotting. C. albicans EVs induced a strong pro-inflammatory response, with increased production of IL-1\u03b2, IL-6, TNF, IL-8, and IFN-\u03b2 after 24 h. In contrast, A. fumigatus EVs elicited a more limited response, characterized by IL-4 production and minimal pro-inflammatory cytokine induction. Both EV populations modulated PRR expression and activated the cGAS\u2013STING\u2013IRF3 axis; however, C. albicans EVs promoted coordinated activation of TLR4, TLR9, and Dectin-1\u2013CARD9 signaling, whereas A. fumigatus EVs downregulated CARD9 and dampened inflammation. These findings demonstrate that fungal EVs differentially shape macrophage responses through species-specific integration of immune sensing pathways.<\/jats:p>","DOI":"10.3390\/jof12080575","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:02:19Z","timestamp":1785830539000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles from Candida albicans and Aspergillus fumigatus Differentially Integrate PRR and cGAS-STING Signaling to Shape Macrophage Responses"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6712-3235","authenticated-orcid":false,"given":"J\u00falia Le\u00e3o","family":"Froldi","sequence":"first","affiliation":[{"name":"Departament of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-8286","authenticated-orcid":false,"given":"Renan E. A.","family":"Piraine","sequence":"additional","affiliation":[{"name":"Departament of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"},{"name":"Institute of Natural Resources, Federal University of Itajub\u00e1, Itajub\u00e1 37500-903, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-1443","authenticated-orcid":false,"given":"Lucas A.","family":"Tavares","sequence":"additional","affiliation":[{"name":"Departament of Cell and Molecular Biology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-8444","authenticated-orcid":false,"given":"Lucas Fabr\u00edcio Bahia","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Departament of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-023X","authenticated-orcid":false,"given":"Patrick","family":"Santos","sequence":"additional","affiliation":[{"name":"Departament of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-3698","authenticated-orcid":false,"given":"Fausto","family":"Almeida","sequence":"additional","affiliation":[{"name":"Departament of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e255080","DOI":"10.1590\/1519-6984.255080","article-title":"Antifungal activity of 2-chloro-N-phenylacetamide: A new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp.","volume":"84","author":"Silva","year":"2024","journal-title":"Braz. 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