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Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better

Most people infected with the fungus Paracoccidioides spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains tha...

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Autores principales: de-Souza-Silva, Calliandra M., Hurtado, Fabián Andrés, Tavares, Aldo Henrique, de Oliveira, Getúlio P., Raiol, Taina, Nishibe, Christiane, Agustinho, Daniel Paiva, Almeida, Nalvo Franco, Walter, Maria Emília Machado Telles, Nicola, André Moraes, Bocca, Anamélia Lorenzetti, Albuquerque, Patrícia, Silva-Pereira, Ildinete
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712260/
https://www.ncbi.nlm.nih.gov/pubmed/33255176
http://dx.doi.org/10.3390/jof6040311
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author de-Souza-Silva, Calliandra M.
Hurtado, Fabián Andrés
Tavares, Aldo Henrique
de Oliveira, Getúlio P.
Raiol, Taina
Nishibe, Christiane
Agustinho, Daniel Paiva
Almeida, Nalvo Franco
Walter, Maria Emília Machado Telles
Nicola, André Moraes
Bocca, Anamélia Lorenzetti
Albuquerque, Patrícia
Silva-Pereira, Ildinete
author_facet de-Souza-Silva, Calliandra M.
Hurtado, Fabián Andrés
Tavares, Aldo Henrique
de Oliveira, Getúlio P.
Raiol, Taina
Nishibe, Christiane
Agustinho, Daniel Paiva
Almeida, Nalvo Franco
Walter, Maria Emília Machado Telles
Nicola, André Moraes
Bocca, Anamélia Lorenzetti
Albuquerque, Patrícia
Silva-Pereira, Ildinete
author_sort de-Souza-Silva, Calliandra M.
collection PubMed
description Most people infected with the fungus Paracoccidioides spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains that are resistant (A/J) or susceptible (B10.A) to P. brasiliensis to study how dendritic cells (DCs) respond to the infection. RNA sequencing analysis showed that the susceptible strain DCs remodeled their transcriptomes much more intensely than those from the resistant strain, agreeing with a previous model of more intense innate immunity response in the susceptible strain. Contrastingly, these cells also repress genes/processes involved in antigen processing and presentation, such as lysosomal activity and autophagy. After the interaction with P. brasiliensis, both DCs and macrophages from the susceptible mouse reduced the autophagy marker LC3-II recruitment to the fungal phagosome compared to the resistant strain cells, confirming this pathway’s repression. These results suggest that impairment in antigen processing and presentation processes might be partially responsible for the inefficient activation of the adaptive immune response in this model.
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spelling pubmed-77122602020-12-04 Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better de-Souza-Silva, Calliandra M. Hurtado, Fabián Andrés Tavares, Aldo Henrique de Oliveira, Getúlio P. Raiol, Taina Nishibe, Christiane Agustinho, Daniel Paiva Almeida, Nalvo Franco Walter, Maria Emília Machado Telles Nicola, André Moraes Bocca, Anamélia Lorenzetti Albuquerque, Patrícia Silva-Pereira, Ildinete J Fungi (Basel) Article Most people infected with the fungus Paracoccidioides spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains that are resistant (A/J) or susceptible (B10.A) to P. brasiliensis to study how dendritic cells (DCs) respond to the infection. RNA sequencing analysis showed that the susceptible strain DCs remodeled their transcriptomes much more intensely than those from the resistant strain, agreeing with a previous model of more intense innate immunity response in the susceptible strain. Contrastingly, these cells also repress genes/processes involved in antigen processing and presentation, such as lysosomal activity and autophagy. After the interaction with P. brasiliensis, both DCs and macrophages from the susceptible mouse reduced the autophagy marker LC3-II recruitment to the fungal phagosome compared to the resistant strain cells, confirming this pathway’s repression. These results suggest that impairment in antigen processing and presentation processes might be partially responsible for the inefficient activation of the adaptive immune response in this model. MDPI 2020-11-24 /pmc/articles/PMC7712260/ /pubmed/33255176 http://dx.doi.org/10.3390/jof6040311 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
de-Souza-Silva, Calliandra M.
Hurtado, Fabián Andrés
Tavares, Aldo Henrique
de Oliveira, Getúlio P.
Raiol, Taina
Nishibe, Christiane
Agustinho, Daniel Paiva
Almeida, Nalvo Franco
Walter, Maria Emília Machado Telles
Nicola, André Moraes
Bocca, Anamélia Lorenzetti
Albuquerque, Patrícia
Silva-Pereira, Ildinete
Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better
title Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better
title_full Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better
title_fullStr Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better
title_full_unstemmed Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better
title_short Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better
title_sort transcriptional remodeling patterns in murine dendritic cells infected with paracoccidioides brasiliensis: more is not necessarily better
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712260/
https://www.ncbi.nlm.nih.gov/pubmed/33255176
http://dx.doi.org/10.3390/jof6040311
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