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

Most people infected with the fungus <i>Paracoccidioides</i> 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 tw...

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Main Authors: Calliandra M. de-Souza-Silva, Fabián Andrés Hurtado, Aldo Henrique Tavares, Getúlio P. de Oliveira, Taina Raiol, Christiane Nishibe, Daniel Paiva Agustinho, Nalvo Franco Almeida, Maria Emília Machado Telles Walter, André Moraes Nicola, Anamélia Lorenzetti Bocca, Patrícia Albuquerque, Ildinete Silva-Pereira
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/6/4/311
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author Calliandra M. de-Souza-Silva
Fabián Andrés Hurtado
Aldo Henrique Tavares
Getúlio P. de Oliveira
Taina Raiol
Christiane Nishibe
Daniel Paiva Agustinho
Nalvo Franco Almeida
Maria Emília Machado Telles Walter
André Moraes Nicola
Anamélia Lorenzetti Bocca
Patrícia Albuquerque
Ildinete Silva-Pereira
author_facet Calliandra M. de-Souza-Silva
Fabián Andrés Hurtado
Aldo Henrique Tavares
Getúlio P. de Oliveira
Taina Raiol
Christiane Nishibe
Daniel Paiva Agustinho
Nalvo Franco Almeida
Maria Emília Machado Telles Walter
André Moraes Nicola
Anamélia Lorenzetti Bocca
Patrícia Albuquerque
Ildinete Silva-Pereira
author_sort Calliandra M. de-Souza-Silva
collection DOAJ
description Most people infected with the fungus <i>Paracoccidioides</i> 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 <i>P. brasiliensis</i> 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 <i>P. brasiliensis</i>, 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 doaj.art-066d3a63c0c74c518e9c8d2512f7d9b02023-11-20T22:04:00ZengMDPI AGJournal of Fungi2309-608X2020-11-016431110.3390/jof6040311Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with <i>Paracoccidioides brasiliensis</i>: More Is Not Necessarily BetterCalliandra M. de-Souza-Silva0Fabián Andrés Hurtado1Aldo Henrique Tavares2Getúlio P. de Oliveira3Taina Raiol4Christiane Nishibe5Daniel Paiva Agustinho6Nalvo Franco Almeida7Maria Emília Machado Telles Walter8André Moraes Nicola9Anamélia Lorenzetti Bocca10Patrícia Albuquerque11Ildinete Silva-Pereira12Laboratory of Molecular Biology of Pathogenic Fungi, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília, DF 70910-900, BrazilLaboratory of Molecular Biology of Pathogenic Fungi, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília, DF 70910-900, BrazilFaculty of Ceilândia, University of Brasília, Brasília, DF 72220-275, BrazilDivision of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAFiocruz Brasília, Oswaldo Cruz Foundation, Brasília, DF 70904-130, BrazilFaculty of Computing, Federal University of Mato Grosso do Sul, Campo Grande, MS 79070-900, BrazilDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110-1093, USAFaculty of Computing, Federal University of Mato Grosso do Sul, Campo Grande, MS 79070-900, BrazilDepartment of Computer Science, University of Brasília, Brasília, DF 70910-900, BrazilFaculty of Medicine, University of Brasília, Brasília, DF 70910-900, BrazilLaboratory of Applied Immunology, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília, DF 70910-900, BrazilLaboratory of Molecular Biology of Pathogenic Fungi, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília, DF 70910-900, BrazilLaboratory of Molecular Biology of Pathogenic Fungi, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília, DF 70910-900, BrazilMost people infected with the fungus <i>Paracoccidioides</i> 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 <i>P. brasiliensis</i> 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 <i>P. brasiliensis</i>, 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.https://www.mdpi.com/2309-608X/6/4/311<i>Paracoccidioides brasiliensis</i>fungal innate immunitydendritic cellsresistancesusceptibilityA/J and B10.A mouse strains
spellingShingle Calliandra M. de-Souza-Silva
Fabián Andrés Hurtado
Aldo Henrique Tavares
Getúlio P. de Oliveira
Taina Raiol
Christiane Nishibe
Daniel Paiva Agustinho
Nalvo Franco Almeida
Maria Emília Machado Telles Walter
André Moraes Nicola
Anamélia Lorenzetti Bocca
Patrícia Albuquerque
Ildinete Silva-Pereira
Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with <i>Paracoccidioides brasiliensis</i>: More Is Not Necessarily Better
Journal of Fungi
<i>Paracoccidioides brasiliensis</i>
fungal innate immunity
dendritic cells
resistance
susceptibility
A/J and B10.A mouse strains
title Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with <i>Paracoccidioides brasiliensis</i>: More Is Not Necessarily Better
title_full Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with <i>Paracoccidioides brasiliensis</i>: More Is Not Necessarily Better
title_fullStr Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with <i>Paracoccidioides brasiliensis</i>: More Is Not Necessarily Better
title_full_unstemmed Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with <i>Paracoccidioides brasiliensis</i>: More Is Not Necessarily Better
title_short Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with <i>Paracoccidioides brasiliensis</i>: More Is Not Necessarily Better
title_sort transcriptional remodeling patterns in murine dendritic cells infected with i paracoccidioides brasiliensis i more is not necessarily better
topic <i>Paracoccidioides brasiliensis</i>
fungal innate immunity
dendritic cells
resistance
susceptibility
A/J and B10.A mouse strains
url https://www.mdpi.com/2309-608X/6/4/311
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