PMID- 33550415 OWN - NLM STAT- MEDLINE DCOM- 20211210 LR - 20220425 IS - 1460-2709 (Electronic) IS - 1369-3786 (Linking) VI - 59 IP - 8 DP - 2021 Jul 14 TI - Zymosan enhances in vitro phagocyte function and the immune response of mice infected with Paracoccidioides brasiliensis. PG - 749-762 LID - 10.1093/mmy/myaa117 [doi] AB - Paracoccidioides brasiliensis is the major etiologic agent of Paracoccidioidomycosis (PCM), the most frequent human deep mycosis in Latin America. It is proposed that masking of beta-glucan in P. brasiliensis cell wall is a critical virulence factor that contributes to the development of a chronic disease characterized by a long period of treatment, which is usually toxic. In this context, the search for immunomodulatory agents for therapeutic purposes is highly desirable. One strategy is to use pattern recognition receptors (PRRs) ligands to stimulate the immune response mediated by phagocytes. Here, we sought to evaluate if Zymosan, a beta-glucan-containing ligand of the PRRs Dectin-1/TLR-2, would enhance phagocyte function and the immune response of mice challenged with P. brasiliensis. Dendritic cells (DCs) infected with P. brasiliensis and treated with Zymosan showed improved secretion of several proinflammatory cytokines and expression of maturation markers. In addition, when cocultured with splenic lymphocytes, these cells induced the production of a potential protective type 1 and 17 cytokine patterns. In macrophages, Zymosan ensued a significant fungicidal activity associated with nitric oxide production and phagolysosome acidification. Importantly, we observed a protective effect of Zymosan-primed DCs delivered intranasally in experimental pulmonary PCM. Overall, our findings support the potential use of beta-glucan-containing compounds such as Zymosan as an alternative or complementary antifungal therapy. LAY SUMMARY: We report for the first time that Paracoccidioides brasiliensis-infected phagocytes treated with Zymosan (cell wall extract from bakers' yeast) show enhanced cytokine production, maturation, and fungal killing. Also, Zymosan-primed phagocytes induce a protective immune response in infected mice. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. FAU - Silva, G S AU - Silva GS AD - Graduate Program in Molecular Pathology, Faculty of Medicine, University of Brasilia, UnB, Brasilia, DF, Brazil. AD - Faculty of Ceilandia, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - Silva, D A AU - Silva DA AD - Faculty of Ceilandia, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - Guilhelmelli, F AU - Guilhelmelli F AD - Laboratory of Molecular Biology of Pathogenic Fungi. Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Jeronimo, M S AU - Jeronimo MS AD - Laboratory of Applied Immunology, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - Cardoso-Miguel, M R D AU - Cardoso-Miguel MRD AD - Graduate Program in Microbial Biology, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - Burgel, P H AU - Burgel PH AD - Laboratory of Applied Immunology, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, UnB, Brasilia, DF, Brazil. AD - Graduate Program in Microbial Biology, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - Castro, R J A AU - Castro RJA AD - Laboratory of Applied Immunology, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - de Oliveira, S A M AU - de Oliveira SAM AD - Laboratory of Applied Immunology, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - Silva-Pereira, I AU - Silva-Pereira I AD - Laboratory of Molecular Biology of Pathogenic Fungi. Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Bocca, A L AU - Bocca AL AD - Laboratory of Applied Immunology, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, UnB, Brasilia, DF, Brazil. FAU - Tavares, A H AU - Tavares AH AD - Faculty of Ceilandia, University of Brasilia, UnB, Brasilia, DF, Brazil. LA - eng PT - Journal Article PL - England TA - Med Mycol JT - Medical mycology JID - 9815835 RN - 9010-72-4 (Zymosan) SB - IM MH - Animals MH - Mice MH - Paracoccidioides/*immunology/pathogenicity MH - Paracoccidioidomycosis/*drug therapy/immunology MH - Phagocytes/*drug effects/immunology MH - Virulence MH - Zymosan/*pharmacology/therapeutic use OTO - NOTNLM OT - Paracoccidioides brasiliensis OT - dendritic cells OT - macrophages OT - zymosan EDAT- 2021/02/08 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/02/07 20:52 PHST- 2020/10/21 00:00 [received] PHST- 2020/12/24 00:00 [accepted] PHST- 2020/11/26 00:00 [revised] PHST- 2021/02/08 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/02/07 20:52 [entrez] AID - 6130099 [pii] AID - 10.1093/mmy/myaa117 [doi] PST - ppublish SO - Med Mycol. 2021 Jul 14;59(8):749-762. doi: 10.1093/mmy/myaa117.