Cargando…

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 Paracoccidioides brasiliensis, 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 m...

Descripción completa

Detalles Bibliográficos
Autores principales: Santos, Suelen S., Rampazo, Eline, Taborda, Carlos P., Nosanchuk, Joshua D., Boscardin, Silvia B., Almeida, Sandro R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219127/
https://www.ncbi.nlm.nih.gov/pubmed/37233259
http://dx.doi.org/10.3390/jof9050548
_version_ 1785048935565361152
author Santos, Suelen S.
Rampazo, Eline
Taborda, Carlos P.
Nosanchuk, Joshua D.
Boscardin, Silvia B.
Almeida, Sandro R.
author_facet Santos, Suelen S.
Rampazo, Eline
Taborda, Carlos P.
Nosanchuk, Joshua D.
Boscardin, Silvia B.
Almeida, Sandro R.
author_sort Santos, Suelen S.
collection PubMed
description Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis, 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(+) helper and CD8(+) 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.
format Online
Article
Text
id pubmed-10219127
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102191272023-05-27 Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis Santos, Suelen S. Rampazo, Eline Taborda, Carlos P. Nosanchuk, Joshua D. Boscardin, Silvia B. Almeida, Sandro R. J Fungi (Basel) Article Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis, 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(+) helper and CD8(+) 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. MDPI 2023-05-10 /pmc/articles/PMC10219127/ /pubmed/37233259 http://dx.doi.org/10.3390/jof9050548 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Santos, Suelen S.
Rampazo, Eline
Taborda, Carlos P.
Nosanchuk, Joshua D.
Boscardin, Silvia B.
Almeida, Sandro R.
Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219127/
https://www.ncbi.nlm.nih.gov/pubmed/37233259
http://dx.doi.org/10.3390/jof9050548
work_keys_str_mv AT santossuelens targetingthep10peptideinmaturingdendriticcellsviathedec205receptorinvivoanewtherapeuticstrategyagainstparacoccidioidomycosis
AT rampazoeline targetingthep10peptideinmaturingdendriticcellsviathedec205receptorinvivoanewtherapeuticstrategyagainstparacoccidioidomycosis
AT tabordacarlosp targetingthep10peptideinmaturingdendriticcellsviathedec205receptorinvivoanewtherapeuticstrategyagainstparacoccidioidomycosis
AT nosanchukjoshuad targetingthep10peptideinmaturingdendriticcellsviathedec205receptorinvivoanewtherapeuticstrategyagainstparacoccidioidomycosis
AT boscardinsilviab targetingthep10peptideinmaturingdendriticcellsviathedec205receptorinvivoanewtherapeuticstrategyagainstparacoccidioidomycosis
AT almeidasandror targetingthep10peptideinmaturingdendriticcellsviathedec205receptorinvivoanewtherapeuticstrategyagainstparacoccidioidomycosis