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Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production

Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii...

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Autores principales: Fernandes, Reginaldo K., Bachiega, Tatiana F., Rodrigues, Daniela R., Golim, Marjorie de A., Dias-Melicio, Luciane A., Balderramas, Helanderson de A., Kaneno, Ramon, Soares, Ângela M. V. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368678/
https://www.ncbi.nlm.nih.gov/pubmed/25793979
http://dx.doi.org/10.1371/journal.pone.0120948
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author Fernandes, Reginaldo K.
Bachiega, Tatiana F.
Rodrigues, Daniela R.
Golim, Marjorie de A.
Dias-Melicio, Luciane A.
Balderramas, Helanderson de A.
Kaneno, Ramon
Soares, Ângela M. V. C.
author_facet Fernandes, Reginaldo K.
Bachiega, Tatiana F.
Rodrigues, Daniela R.
Golim, Marjorie de A.
Dias-Melicio, Luciane A.
Balderramas, Helanderson de A.
Kaneno, Ramon
Soares, Ângela M. V. C.
author_sort Fernandes, Reginaldo K.
collection PubMed
description Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE(2), which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE(2) inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE(2) confirmed an association between PGE(2) inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.
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spelling pubmed-43686782015-03-27 Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production Fernandes, Reginaldo K. Bachiega, Tatiana F. Rodrigues, Daniela R. Golim, Marjorie de A. Dias-Melicio, Luciane A. Balderramas, Helanderson de A. Kaneno, Ramon Soares, Ângela M. V. C. PLoS One Research Article Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE(2), which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE(2) inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE(2) confirmed an association between PGE(2) inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus. Public Library of Science 2015-03-20 /pmc/articles/PMC4368678/ /pubmed/25793979 http://dx.doi.org/10.1371/journal.pone.0120948 Text en © 2015 Fernandes et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fernandes, Reginaldo K.
Bachiega, Tatiana F.
Rodrigues, Daniela R.
Golim, Marjorie de A.
Dias-Melicio, Luciane A.
Balderramas, Helanderson de A.
Kaneno, Ramon
Soares, Ângela M. V. C.
Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production
title Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production
title_full Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production
title_fullStr Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production
title_full_unstemmed Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production
title_short Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE(2) Production
title_sort paracoccidioides brasiliensis interferes on dendritic cells maturation by inhibiting pge(2) production
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368678/
https://www.ncbi.nlm.nih.gov/pubmed/25793979
http://dx.doi.org/10.1371/journal.pone.0120948
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