PMID- 34359982 OWN - NLM STAT- MEDLINE DCOM- 20211026 LR - 20240226 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 10 IP - 7 DP - 2021 Jul 17 TI - Protective Response in Experimental Paracoccidioidomycosis Elicited by Extracellular Vesicles Containing Antigens of Paracoccidioides brasiliensis. LID - 10.3390/cells10071813 [doi] LID - 1813 AB - Paracoccidioidomycosis (PCM) is a systemic disease caused by Paracoccidioides spp. PCM is endemic in Latin America and most cases are registered in Brazil. This mycosis affects mainly the lungs, but can also spread to other tissues and organs, including the liver. Several approaches have been investigated to improve treatment effectiveness and protection against the disease. Extracellular vesicles (EVs) are good antigen delivery vehicles. The present work aims to investigate the use of EVs derived from Paracoccidioides brasiliensis as an immunization tool in a murine model of PCM. For this, male C57BL/6 were immunized with two doses of EVs plus adjuvant and then infected with P. brasiliensis. EV immunization induced IgM and IgG in vivo and cytokine production by splenocytes ex vivo. Further, immunization with EVs had a positive effect on mice infected with P. brasiliensis, as it induced activated T lymphocytes and NKT cell mobilization to the infected lungs, improved production of proinflammatory cytokines and the histopathological profile, and reduced fungal burden. Therefore, the present study shows a new role for P. brasiliensis EVs in the presence of adjuvant as modulators of the host immune system, suggesting their utility as immunizing agents. FAU - Baltazar, Ludmila Matos AU - Baltazar LM AD - Laboratorio de Interacao Microrganismo Hospedeiro, Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. FAU - Ribeiro, Gabriela Fior AU - Ribeiro GF AD - Laboratorio de Interacao Microrganismo Hospedeiro, Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. FAU - Freitas, Gustavo J AU - Freitas GJ AD - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. FAU - Queiroz-Junior, Celso Martins AU - Queiroz-Junior CM AD - Departamento de Morfologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. FAU - Fagundes, Caio Tavares AU - Fagundes CT AUID- ORCID: 0000-0002-6747-5233 AD - Laboratorio de Interacao Microrganismo Hospedeiro, Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. FAU - Chaves-Olortegui, Carlos AU - Chaves-Olortegui C AD - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. FAU - Teixeira, Mauro Martins AU - Teixeira MM AD - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. FAU - Souza, Daniele G AU - Souza DG AUID- ORCID: 0000-0002-7478-5934 AD - Laboratorio de Interacao Microrganismo Hospedeiro, Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 6627, Antonio Carlos Ave, Belo Horizonte, Minas Gerais 31270-901, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210717 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Antibodies, Fungal) RN - 0 (Antigens, Fungal) RN - 0 (Cytokines) RN - 0 (Protective Agents) SB - IM MH - Animals MH - Antibodies, Fungal/immunology MH - Antigens, Fungal/*immunology MH - Cell Movement MH - Cytokines/metabolism MH - Extracellular Vesicles/drug effects/*microbiology MH - Immunization MH - Immunologic Memory MH - Lung/microbiology/pathology MH - Lymphocyte Activation/immunology MH - Male MH - Mice, Inbred C57BL MH - Natural Killer T-Cells/immunology MH - Paracoccidioides/*immunology MH - Paracoccidioidomycosis/*immunology/*microbiology MH - Protective Agents/*pharmacology MH - Reference Standards MH - Mice PMC - PMC8304155 OTO - NOTNLM OT - Paracoccidioides brasiliensis OT - extracellular vesicles OT - host response OT - immunization COIS- The authors declare no conflict of interest. EDAT- 2021/08/08 06:00 MHDA- 2021/10/27 06:00 PMCR- 2021/07/17 CRDT- 2021/08/07 01:04 PHST- 2021/06/13 00:00 [received] PHST- 2021/07/10 00:00 [revised] PHST- 2021/07/13 00:00 [accepted] PHST- 2021/08/07 01:04 [entrez] PHST- 2021/08/08 06:00 [pubmed] PHST- 2021/10/27 06:00 [medline] PHST- 2021/07/17 00:00 [pmc-release] AID - cells10071813 [pii] AID - cells-10-01813 [pii] AID - 10.3390/cells10071813 [doi] PST - epublish SO - Cells. 2021 Jul 17;10(7):1813. doi: 10.3390/cells10071813.