PMID- 31417520 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 10 DP - 2019 TI - Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice. PG - 1727 LID - 10.3389/fmicb.2019.01727 [doi] LID - 1727 AB - 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 naive 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 Th(1)/Th(2) 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. FAU - Silva, Leandro B R AU - Silva LBR AD - USP-LIM53, Laboratory of Medical Mycology, Institute of Tropical Medicine, University of Sao Paulo, Sao Paulo, Brazil. FAU - Taira, Cleison L AU - Taira CL AD - Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Dias, Lucas S AU - Dias LS AD - Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Souza, Ana C O AU - Souza ACO AD - Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Nosanchuk, Joshua D AU - Nosanchuk JD AD - Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, United States. FAU - Travassos, Luiz R AU - Travassos LR AD - Department of Microbiology, Immunology and Parasitology, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Taborda, Carlos P AU - Taborda CP AD - USP-LIM53, Laboratory of Medical Mycology, Institute of Tropical Medicine, University of Sao Paulo, Sao Paulo, Brazil. AD - Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. LA - eng GR - R01 AI052733/AI/NIAID NIH HHS/United States GR - R21 AI124797/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20190731 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC6685297 OTO - NOTNLM OT - dendritic cells OT - monocyte-derived dendritic cells OT - paracoccidioidomycosis OT - peptide P10 OT - vaccine EDAT- 2019/08/17 06:00 MHDA- 2019/08/17 06:01 PMCR- 2019/07/31 CRDT- 2019/08/17 06:00 PHST- 2019/04/25 00:00 [received] PHST- 2019/07/12 00:00 [accepted] PHST- 2019/08/17 06:00 [entrez] PHST- 2019/08/17 06:00 [pubmed] PHST- 2019/08/17 06:01 [medline] PHST- 2019/07/31 00:00 [pmc-release] AID - 10.3389/fmicb.2019.01727 [doi] PST - epublish SO - Front Microbiol. 2019 Jul 31;10:1727. doi: 10.3389/fmicb.2019.01727. eCollection 2019.