Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response
Granulomas are important immunological structures in the host defense against the fungus Paracoccidioides brasiliensis, the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous systemic mycosis endemic in Latin America. We have performed transcriptional and proteomic studies of yeas...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1268959/full |
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| author | Bruno Montanari Borges Rafael Berton Correia Ramos Nycolas Willian Preite Valéria de Lima Kaminski Patrícia Alves de Castro Maurício Camacho Marina Ferreira Maximo Taicia Pacheco Fill Vera Lúcia Garcia Calich Aimee M. Traynor Özlem Sarikaya-Bayram Sean Doyle Özgür Bayram Claudia Barbosa Ladeira de Campos André Zelanis Gustavo H. Goldman Flávio Vieira Loures |
| author_facet | Bruno Montanari Borges Rafael Berton Correia Ramos Nycolas Willian Preite Valéria de Lima Kaminski Patrícia Alves de Castro Maurício Camacho Marina Ferreira Maximo Taicia Pacheco Fill Vera Lúcia Garcia Calich Aimee M. Traynor Özlem Sarikaya-Bayram Sean Doyle Özgür Bayram Claudia Barbosa Ladeira de Campos André Zelanis Gustavo H. Goldman Flávio Vieira Loures |
| author_sort | Bruno Montanari Borges |
| collection | DOAJ |
| description | Granulomas are important immunological structures in the host defense against the fungus Paracoccidioides brasiliensis, the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous systemic mycosis endemic in Latin America. We have performed transcriptional and proteomic studies of yeasts present in the pulmonary granulomas of PCM aiming to identify relevant genes and proteins that act under stressing conditions. C57BL/6 mice were infected with 1x106 yeasts and after 8- and 12-weeks of infection, granulomatous lesions were obtained for extraction of fungal and murine RNAs and fungal proteins. Dual transcriptional profiling was done comparing lung cells and P. brasiliensis yeasts from granulomas with uninfected lung cells and the original yeast suspension used in the infection, respectively. Mouse transcripts indicated a lung malfunction, with low expression of genes related to muscle contraction and organization. In addition, an increased expression of transcripts related to the activity of neutrophils, eosinophils, macrophages, lymphocytes as well as an elevated expression of IL-1β, TNF-α, IFN-γ, IL-17 transcripts were observed. The increased expression of transcripts for CTLA-4, PD-1 and arginase-1, provided evidence of immune regulatory mechanisms within the granulomatous lesions. Also, our results indicate iron as a key element for the granuloma to function, where a high number of transcripts related to fungal siderophores for iron uptake was observed, a mechanism of fungal virulence not previously described in granulomas. Furthermore, transcriptomics and proteomics analyzes indicated a low fungal activity within the granuloma, as demonstrated by the decreased expression of genes and proteins related to energy metabolism and cell cycle. |
| first_indexed | 2024-03-11T19:49:24Z |
| format | Article |
| id | doaj.art-68a73958ff004898a97f1b937a00e98a |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-11T19:49:24Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-68a73958ff004898a97f1b937a00e98a2023-10-05T13:17:46ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-10-011310.3389/fcimb.2023.12689591268959Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune responseBruno Montanari Borges0Rafael Berton Correia Ramos1Nycolas Willian Preite2Valéria de Lima Kaminski3Patrícia Alves de Castro4Maurício Camacho5Marina Ferreira Maximo6Taicia Pacheco Fill7Vera Lúcia Garcia Calich8Aimee M. Traynor9Özlem Sarikaya-Bayram10Sean Doyle11Özgür Bayram12Claudia Barbosa Ladeira de Campos13André Zelanis14Gustavo H. Goldman15Flávio Vieira Loures16Institute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilInstitute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilInstitute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilInstitute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilFaculty of Pharmaceutical Science of Ribeirão Preto (FCFRP), University of São Paulo (USP), Ribeirão Preto, SP, BrazilInstitute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilInstitute of Chemistry, Universidade Estadual de Campinas, Campinas, SP, BrazilInstitute of Chemistry, Universidade Estadual de Campinas, Campinas, SP, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, BrazilDepartment of Biology, Maynooth University, Maynooth, County Kildare, IrelandDepartment of Biology, Maynooth University, Maynooth, County Kildare, IrelandDepartment of Biology, Maynooth University, Maynooth, County Kildare, IrelandDepartment of Biology, Maynooth University, Maynooth, County Kildare, IrelandInstitute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilInstitute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilFaculty of Pharmaceutical Science of Ribeirão Preto (FCFRP), University of São Paulo (USP), Ribeirão Preto, SP, BrazilInstitute of Science and Technology (ICT), Federal University of São Paulo (UNIFESP), São José dos Campos, SP, BrazilGranulomas are important immunological structures in the host defense against the fungus Paracoccidioides brasiliensis, the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous systemic mycosis endemic in Latin America. We have performed transcriptional and proteomic studies of yeasts present in the pulmonary granulomas of PCM aiming to identify relevant genes and proteins that act under stressing conditions. C57BL/6 mice were infected with 1x106 yeasts and after 8- and 12-weeks of infection, granulomatous lesions were obtained for extraction of fungal and murine RNAs and fungal proteins. Dual transcriptional profiling was done comparing lung cells and P. brasiliensis yeasts from granulomas with uninfected lung cells and the original yeast suspension used in the infection, respectively. Mouse transcripts indicated a lung malfunction, with low expression of genes related to muscle contraction and organization. In addition, an increased expression of transcripts related to the activity of neutrophils, eosinophils, macrophages, lymphocytes as well as an elevated expression of IL-1β, TNF-α, IFN-γ, IL-17 transcripts were observed. The increased expression of transcripts for CTLA-4, PD-1 and arginase-1, provided evidence of immune regulatory mechanisms within the granulomatous lesions. Also, our results indicate iron as a key element for the granuloma to function, where a high number of transcripts related to fungal siderophores for iron uptake was observed, a mechanism of fungal virulence not previously described in granulomas. Furthermore, transcriptomics and proteomics analyzes indicated a low fungal activity within the granuloma, as demonstrated by the decreased expression of genes and proteins related to energy metabolism and cell cycle.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1268959/fullparacoccidioidomycosisgranulomatranscriptomicproteomicfungal infection |
| spellingShingle | Bruno Montanari Borges Rafael Berton Correia Ramos Nycolas Willian Preite Valéria de Lima Kaminski Patrícia Alves de Castro Maurício Camacho Marina Ferreira Maximo Taicia Pacheco Fill Vera Lúcia Garcia Calich Aimee M. Traynor Özlem Sarikaya-Bayram Sean Doyle Özgür Bayram Claudia Barbosa Ladeira de Campos André Zelanis Gustavo H. Goldman Flávio Vieira Loures Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response Frontiers in Cellular and Infection Microbiology paracoccidioidomycosis granuloma transcriptomic proteomic fungal infection |
| title | Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response |
| title_full | Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response |
| title_fullStr | Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response |
| title_full_unstemmed | Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response |
| title_short | Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response |
| title_sort | transcriptional profiling of a fungal granuloma reveals a low metabolic activity of paracoccidioides brasiliensis yeasts and an actively regulated host immune response |
| topic | paracoccidioidomycosis granuloma transcriptomic proteomic fungal infection |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1268959/full |
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