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Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice.
Front Microbiol 2019; 10:1727FM

Abstract

Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin American caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Notably, a Th1 immune response is required to control PCM. In this context, dendritic cells (DCs) seem to be essential players in capture, processing and presentation of Paracoccidioides antigens to naïve T cells and their further activation. We have previously demonstrated that differentiated DCs from bone marrow cells, pulsed with the immunoprotective peptide 10 (P10), effectively control experimental PCM immunocompetent and immunosuppressed mice. However, this procedure may not be infeasible or it is limited for the therapy of human patients. Therefore, we have sought a less invasive but equally effective approach that would better mimics the autologous transplant of DC in a human patient. Here, we isolated and generated monocyte differentiated dendritic cells (MoDCs) from infected mice, pulsed them with P-10, and used them in the therapy of PCM in syngeneic mice. Similar to the results using BMDCs, the P10-pulsed MoDCs stimulated the proliferation of CD4+ T lymphocytes, induced a mixed production of Th1/Th2 cytokines and decreased the fungal burden in murine lungs in the setting of PCM. The process of differentiating MoDCs derived from an infected host, and subsequently used for therapy of PCM is much simpler than that for obtaining BMDCs, and represents a more reasonable approach to treat patients infected with Paracoccidioides. The results presented suggest that P10-primed MoDC may be a promising strategy to combat complicated PCM as well as to significantly shorten the lengthy requirements for treatment of patients with this fungal disease.

Authors+Show Affiliations

USP-LIM53, Laboratory of Medical Mycology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, United States.Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, Brazil.USP-LIM53, Laboratory of Medical Mycology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31417520

Citation

Silva, Leandro B R., et al. "Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice." Frontiers in Microbiology, vol. 10, 2019, p. 1727.
Silva LBR, Taira CL, Dias LS, et al. Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice. Front Microbiol. 2019;10:1727.
Silva, L. B. R., Taira, C. L., Dias, L. S., Souza, A. C. O., Nosanchuk, J. D., Travassos, L. R., & Taborda, C. P. (2019). Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice. Frontiers in Microbiology, 10, p. 1727. doi:10.3389/fmicb.2019.01727.
Silva LBR, et al. Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice. Front Microbiol. 2019;10:1727. PubMed PMID: 31417520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice. AU - Silva,Leandro B R, AU - Taira,Cleison L, AU - Dias,Lucas S, AU - Souza,Ana C O, AU - Nosanchuk,Joshua D, AU - Travassos,Luiz R, AU - Taborda,Carlos P, Y1 - 2019/07/31/ PY - 2019/04/25/received PY - 2019/07/12/accepted PY - 2019/8/17/entrez PY - 2019/8/17/pubmed PY - 2019/8/17/medline KW - dendritic cells KW - monocyte-derived dendritic cells KW - paracoccidioidomycosis KW - peptide P10 KW - vaccine SP - 1727 EP - 1727 JF - Frontiers in microbiology JO - Front Microbiol VL - 10 N2 - Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin American caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Notably, a Th1 immune response is required to control PCM. In this context, dendritic cells (DCs) seem to be essential players in capture, processing and presentation of Paracoccidioides antigens to naïve T cells and their further activation. We have previously demonstrated that differentiated DCs from bone marrow cells, pulsed with the immunoprotective peptide 10 (P10), effectively control experimental PCM immunocompetent and immunosuppressed mice. However, this procedure may not be infeasible or it is limited for the therapy of human patients. Therefore, we have sought a less invasive but equally effective approach that would better mimics the autologous transplant of DC in a human patient. Here, we isolated and generated monocyte differentiated dendritic cells (MoDCs) from infected mice, pulsed them with P-10, and used them in the therapy of PCM in syngeneic mice. Similar to the results using BMDCs, the P10-pulsed MoDCs stimulated the proliferation of CD4+ T lymphocytes, induced a mixed production of Th1/Th2 cytokines and decreased the fungal burden in murine lungs in the setting of PCM. The process of differentiating MoDCs derived from an infected host, and subsequently used for therapy of PCM is much simpler than that for obtaining BMDCs, and represents a more reasonable approach to treat patients infected with Paracoccidioides. The results presented suggest that P10-primed MoDC may be a promising strategy to combat complicated PCM as well as to significantly shorten the lengthy requirements for treatment of patients with this fungal disease. SN - 1664-302X UR - https://www.unboundmedicine.com/medline/citation/31417520/Experimental_Therapy_of_Paracoccidioidomycosis_Using_P10-Primed_Monocyte-Derived_Dendritic_Cells_Isolated_From_Infected_Mice L2 - https://doi.org/10.3389/fmicb.2019.01727 DB - PRIME DP - Unbound Medicine ER -