Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis
Paracoccidioidomycosis (PCM) is a systemic mycosis caused by <i>Paracoccidioides brasiliensis</i>, a thermally dimorphic fungus, which is the most frequent endemic systemic mycosis in many Latin American countries, where ~10 million people are believed to be infected. In Brazil, it is ra...
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MDPI AG
2023-05-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/5/548 |
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| author | Suelen S. Santos Eline Rampazo Carlos P. Taborda Joshua D. Nosanchuk Silvia B. Boscardin Sandro R. Almeida |
| author_facet | Suelen S. Santos Eline Rampazo Carlos P. Taborda Joshua D. Nosanchuk Silvia B. Boscardin Sandro R. Almeida |
| author_sort | Suelen S. Santos |
| collection | DOAJ |
| description | Paracoccidioidomycosis (PCM) is a systemic mycosis caused by <i>Paracoccidioides brasiliensis</i>, a thermally dimorphic fungus, which is the most frequent endemic systemic mycosis in many Latin American countries, where ~10 million people are believed to be infected. In Brazil, it is ranked as the tenth most common cause of death among chronic infectious diseases. Hence, vaccines are in development to combat this insidious pathogen. It is likely that effective vaccines will need to elicit strong T cell-mediated immune responses composed of IFNγ secreting CD4<sup>+</sup> helper and CD8<sup>+</sup> cytolytic T lymphocytes. To induce such responses, it would be valuable to harness the dendritic cell (DC) system of antigen-presenting cells. To assess the potential of targeting P10, which is a peptide derived from gp43 secreted by the fungus, directly to DCs, we cloned the P10 sequence in fusion with a monoclonal antibody to the DEC205 receptor, an endocytic receptor that is abundant on DCs in lymphoid tissues. We verified that a single injection of the αDEC/P10 antibody caused DCs to produce a large amount of IFNγ. Administration of the chimeric antibody to mice resulted in a significant increase in the levels of IFN-γ and IL-4 in lung tissue relative to control animals. In therapeutic assays, mice pretreated with αDEC/P10 had significantly lower fungal burdens compared to control infected mice, and the architecture of the pulmonary tissues of αDEC/P10 chimera-treated mice was largely normal. Altogether, the results obtained so far indicate that targeting P10 through a αDEC/P10 chimeric antibody in the presence of polyriboinosinic: polyribocytidylic acid is a promising strategy in vaccination and therapeutic protocols to combat PCM. |
| first_indexed | 2024-03-11T03:35:59Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-11T03:35:59Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-dd1a5b0031a143d481fe46e42ca89bc12023-11-18T02:02:08ZengMDPI AGJournal of Fungi2309-608X2023-05-019554810.3390/jof9050548Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against ParacoccidioidomycosisSuelen S. Santos0Eline Rampazo1Carlos P. Taborda2Joshua D. Nosanchuk3Silvia B. Boscardin4Sandro R. Almeida5Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, BrazilDepartment of Parasitology, Biomedical Sciences Institute, University of São Paulo, São Paulo 05508-000, SP, BrazilDepartment of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo 05508-000, SP, BrazilDepartments of Medicine, Division of Infectious Diseases, Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USADepartment of Parasitology, Biomedical Sciences Institute, University of São Paulo, São Paulo 05508-000, SP, BrazilDepartment of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, BrazilParacoccidioidomycosis (PCM) is a systemic mycosis caused by <i>Paracoccidioides brasiliensis</i>, a thermally dimorphic fungus, which is the most frequent endemic systemic mycosis in many Latin American countries, where ~10 million people are believed to be infected. In Brazil, it is ranked as the tenth most common cause of death among chronic infectious diseases. Hence, vaccines are in development to combat this insidious pathogen. It is likely that effective vaccines will need to elicit strong T cell-mediated immune responses composed of IFNγ secreting CD4<sup>+</sup> helper and CD8<sup>+</sup> cytolytic T lymphocytes. To induce such responses, it would be valuable to harness the dendritic cell (DC) system of antigen-presenting cells. To assess the potential of targeting P10, which is a peptide derived from gp43 secreted by the fungus, directly to DCs, we cloned the P10 sequence in fusion with a monoclonal antibody to the DEC205 receptor, an endocytic receptor that is abundant on DCs in lymphoid tissues. We verified that a single injection of the αDEC/P10 antibody caused DCs to produce a large amount of IFNγ. Administration of the chimeric antibody to mice resulted in a significant increase in the levels of IFN-γ and IL-4 in lung tissue relative to control animals. In therapeutic assays, mice pretreated with αDEC/P10 had significantly lower fungal burdens compared to control infected mice, and the architecture of the pulmonary tissues of αDEC/P10 chimera-treated mice was largely normal. Altogether, the results obtained so far indicate that targeting P10 through a αDEC/P10 chimeric antibody in the presence of polyriboinosinic: polyribocytidylic acid is a promising strategy in vaccination and therapeutic protocols to combat PCM.https://www.mdpi.com/2309-608X/9/5/548<i>Paracoccidioides brasiliensis</i>paracoccidioidomycosisdendritic cellsDEC205P10 peptide |
| spellingShingle | Suelen S. Santos Eline Rampazo Carlos P. Taborda Joshua D. Nosanchuk Silvia B. Boscardin Sandro R. Almeida Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis Journal of Fungi <i>Paracoccidioides brasiliensis</i> paracoccidioidomycosis dendritic cells DEC205 P10 peptide |
| title | Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis |
| title_full | Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis |
| title_fullStr | Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis |
| title_full_unstemmed | Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis |
| title_short | Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis |
| title_sort | targeting the p10 peptide in maturing dendritic cells via the dec205 receptor in vivo a new therapeutic strategy against paracoccidioidomycosis |
| topic | <i>Paracoccidioides brasiliensis</i> paracoccidioidomycosis dendritic cells DEC205 P10 peptide |
| url | https://www.mdpi.com/2309-608X/9/5/548 |
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