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Inst. Oswaldo Cruz"],"abstract":"<jats:p>BACKGROUND Paracoccidioidomycosis (PCM) is a systemic infection that is endemic to Latin America, caused by thermodimorphic fungi from the Paracoccidioides genus. These fungi are facultative intracellular parasites of macrophages. LC3-associated phagocytosis (LAP), a non-canonical form of autophagy, plays a critical role in the response of these phagocytes to similar pathogens.  OBJECTIVES In this study, we investigated the role of LAP in the macrophage responses to Paracoccidioides spp.  METHODS We detected LAP in macrophages infected with Paracoccidioides spp by immunofluorescence microscopy with antibodies to LC3. Piceatannol and diphenyleneiodonium chloride (DPI), respectively Syk and nicotinamide adenine dinucleotide phosphate oxidase (NADPH) inhibitors, were used to understand the role their pathways played. To determine the function of LAP, we targeted ATG5, a key autophagy gene, by RNA interference.  FINDINGS We observed LC3 recruitment to phagosomes containing Paracoccidioides spp. in RAW264.7 and J774.16 cell lines and in bone marrow-derived macrophages. ATG5 RNA interference reduced the antifungal activity of J774.16 cells, highlighting the importance of LC3 recruitment for effective fungal control. Interestingly, pharmacological inhibition of Syk kinase and NADPH oxidase pathways, essential for LAP against Aspergillus fumigatus and Candida albicans, did not impair LAP against P. brasiliensis.  MAIN CONCLUSIONS This suggests distinct triggering mechanisms, possibly due to differences in the fungal cell surface composition. These findings suggest that LAP plays a significant role in the host defense against Paracoccidioides spp. and may represent a promising target for host-directed PCM therapies.<\/jats:p>","DOI":"10.1590\/0074-02760250089","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:13:18Z","timestamp":1772460798000},"source":"Crossref","is-referenced-by-count":0,"title":["LC3-associated phagocytosis in macrophage responses to Paracoccidioides spp."],"prefix":"10.1590","volume":"121","author":[{"given":"Get\u00falio Pereira","family":"de Oliveira J\u00fanior","sequence":"first","affiliation":[{"name":"Northeastern University,  USA; Universidade Cat\u00f3lica de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herdson Renney","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaio C\u00e9sar de Melo","family":"Gorgonha","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara La\u00eds Montalv\u00e3o","family":"Tomaz","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana Karla dos Santos","family":"Borges","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kellyanne Teixeira","family":"Rangel","sequence":"additional","affiliation":[{"name":"Universidade Cat\u00f3lica de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Fabricant","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Koser 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Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Johns Hopkins University,  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildinete","family":"Silva-Pereira","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Sueli Soares","family":"Felipe","sequence":"additional","affiliation":[{"name":"Universidade Cat\u00f3lica de Bras\u00edlia,  Brasil; Universidade de Bras\u00edlia,  Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia,  Brasil; Cornell University,  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8656-5835","authenticated-orcid":false,"given":"Andr\u00e9 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