PMID- 35755848 OWN - NLM STAT- MEDLINE DCOM- 20220628 LR - 20220805 IS - 2235-2988 (Electronic) IS - 2235-2988 (Linking) VI - 12 DP - 2022 TI - Pathogenicity and Growth Conditions Modulate Fonsecaea Extracellular Vesicles' Ability to Interact With Macrophages. PG - 879018 LID - 10.3389/fcimb.2022.879018 [doi] LID - 879018 AB - Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous mycosis caused by black, dimorphic, and filamentous fungi of the Herpothrichiellaceae family, such as species of the genus Fonsecaea. These fungi can switch between the saprophytic forms (conidia and hyphae) and the pathogenic form, the muriform cells (MCs), which is considered an essential mechanism for fungal virulence. Nearly all types of cells can produce membranous structures formed by a lipid bilayer that communicate extracellularly with other cells, known as "extracellular vesicles" (EVs), which may act as virulence factors, as observed for several species of pathogenic fungi. Our findings demonstrated for the first time that F. pedrosoi, F. nubica, and F. erecta produce EVs in response to nutritional conditions. The EVs varied in sterol and protein contents, size, and morphology. Moreover, the EVs induced different cytokine and nitric oxide release patterns by bone marrow-derived macrophages (BMDMs). The EVs activated IL-1beta production, possibly acting as the first signal in inflammasome activation. Unlike the pathogenic species, the EVs isolated from F. erecta did not significantly stimulate TNF and IL-10 production in general. Overall, these results demonstrated that different species of Fonsecaea produce EVs capable of modulating pro- and anti-inflammatory cytokine and nitric oxide production by BMDMs and that growth conditions affected the immunomodulatory capacities of the EVs as well as their size, content, and morphology. CI - Copyright (c) 2022 Las-Casas, Marina, de Castro, Coelho, Bao, de Hoog, Vicente, Fernandes and Bocca. FAU - Las-Casas, Lucas de Oliveira AU - Las-Casas LO AD - Department of Cell Biology, University of Brasilia, Brasilia, Brazil. FAU - Marina, Clara Luna Freitas AU - Marina CLF AD - Department of Cell Biology, University of Brasilia, Brasilia, Brazil. FAU - de Castro, Raffael Junio Araujo AU - de Castro RJA AD - Department of Cell Biology, University of Brasilia, Brasilia, Brazil. FAU - Coelho, Luisa Coutinho AU - Coelho LC AD - Department of Cell Biology, University of Brasilia, Brasilia, Brazil. FAU - Bao, Sonia Nair AU - Bao SN AD - Department of Cell Biology, University of Brasilia, Brasilia, Brazil. FAU - de Hoog, G Sybren AU - de Hoog GS AD - Department of Pathology, Federal University of Parana, Curitiba, Brazil. AD - Center of Expertise in Mycology of Radboud, University Medical Center/Canisius Wilhelmina Hospital, Nijmegen, Netherlands. FAU - Vicente, Vania Aparecida AU - Vicente VA AD - Department of Pathology, Federal University of Parana, Curitiba, Brazil. FAU - Fernandes, Larissa AU - Fernandes L AD - Faculty of Ceilandia, University of Brasilia, Brasilia, Brazil. FAU - Bocca, Anamelia Lorenzetti AU - Bocca AL AD - Department of Cell Biology, University of Brasilia, Brasilia, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220609 PL - Switzerland TA - Front Cell Infect Microbiol JT - Frontiers in cellular and infection microbiology JID - 101585359 RN - 0 (Cytokines) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - *Ascomycota MH - *Chromoblastomycosis/microbiology/pathology MH - Cytokines MH - *Extracellular Vesicles MH - Fonsecaea MH - Macrophages MH - Nitric Oxide MH - Virulence PMC - PMC9218254 OTO - NOTNLM OT - Fonsecaea OT - chromoblastomycosis OT - extracellular vesicles OT - macrophages OT - muriform cells COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/28 06:00 MHDA- 2022/06/29 06:00 PMCR- 2022/01/01 CRDT- 2022/06/27 03:55 PHST- 2022/02/18 00:00 [received] PHST- 2022/04/29 00:00 [accepted] PHST- 2022/06/27 03:55 [entrez] PHST- 2022/06/28 06:00 [pubmed] PHST- 2022/06/29 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fcimb.2022.879018 [doi] PST - epublish SO - Front Cell Infect Microbiol. 2022 Jun 9;12:879018. doi: 10.3389/fcimb.2022.879018. eCollection 2022.