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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| Veröffentlicht in: | Journal of fungi (Basel) 2020-11, Vol.6 (4), p.311, Article 311 |
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| creator | de-Souza-Silva, Calliandra M. Hurtado, Fabian Andres Tavares, Aldo Henrique de Oliveira Jr, Getulio P. Raiol, Taina Nishibe, Christiane Agustinho, Daniel Paiva Almeida, Nalvo Franco Machado Telles Walter, Maria Emilia Nicola, Andre Moraes Bocca, Anamelia Lorenzetti Albuquerque, Patricia Silva-Pereira, Ildinete |
| 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. |
| doi_str_mv | 10.3390/jof6040311 |
| format | Article |
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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.</description><identifier>ISSN: 2309-608X</identifier><identifier>EISSN: 2309-608X</identifier><identifier>DOI: 10.3390/jof6040311</identifier><identifier>PMID: 33255176</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>A/J and B10.A mouse strains ; Adaptive immunity ; Antigen presentation ; Antigen processing ; Antigens ; Autophagy ; Bone marrow ; Chemokines ; Cytokines ; Dendritic cells ; Disease ; Experiments ; Fungal infections ; fungal innate immunity ; Fungi ; Gene expression ; Immune system ; Immunology ; Innate immunity ; Life Sciences & Biomedicine ; Macrophages ; Microbiology ; Mycology ; Paracoccidioides brasiliensis ; Pathogens ; Phagocytosis ; resistance ; Ribonucleic acid ; RNA ; Science & Technology ; Sequence analysis ; South American blastomycosis ; susceptibility ; Transcription ; Virulence</subject><ispartof>Journal of fungi (Basel), 2020-11, Vol.6 (4), p.311, Article 311</ispartof><rights>2020. 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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.</description><subject>A/J and B10.A mouse strains</subject><subject>Adaptive immunity</subject><subject>Antigen presentation</subject><subject>Antigen processing</subject><subject>Antigens</subject><subject>Autophagy</subject><subject>Bone marrow</subject><subject>Chemokines</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Disease</subject><subject>Experiments</subject><subject>Fungal infections</subject><subject>fungal innate immunity</subject><subject>Fungi</subject><subject>Gene expression</subject><subject>Immune system</subject><subject>Immunology</subject><subject>Innate immunity</subject><subject>Life Sciences & Biomedicine</subject><subject>Macrophages</subject><subject>Microbiology</subject><subject>Mycology</subject><subject>Paracoccidioides brasiliensis</subject><subject>Pathogens</subject><subject>Phagocytosis</subject><subject>resistance</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Science & Technology</subject><subject>Sequence analysis</subject><subject>South American 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Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better</title><author>de-Souza-Silva, Calliandra M. ; Hurtado, Fabian Andres ; Tavares, Aldo Henrique ; de Oliveira Jr, Getulio P. ; Raiol, Taina ; Nishibe, Christiane ; Agustinho, Daniel Paiva ; Almeida, Nalvo Franco ; Machado Telles Walter, Maria Emilia ; Nicola, Andre Moraes ; Bocca, Anamelia Lorenzetti ; Albuquerque, Patricia ; Silva-Pereira, Ildinete</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-b9152fd5f0ce00691897d5ceaecb31d594a0c49c756ee083e4e201c148d83f6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>A/J and B10.A mouse strains</topic><topic>Adaptive immunity</topic><topic>Antigen presentation</topic><topic>Antigen processing</topic><topic>Antigens</topic><topic>Autophagy</topic><topic>Bone 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| source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | A/J and B10.A mouse strains Adaptive immunity Antigen presentation Antigen processing Antigens Autophagy Bone marrow Chemokines Cytokines Dendritic cells Disease Experiments Fungal infections fungal innate immunity Fungi Gene expression Immune system Immunology Innate immunity Life Sciences & Biomedicine Macrophages Microbiology Mycology Paracoccidioides brasiliensis Pathogens Phagocytosis resistance Ribonucleic acid RNA Science & Technology Sequence analysis South American blastomycosis susceptibility Transcription Virulence |
| title | Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better |
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