rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB.
BACKGROUND:The fungus Paracoccidioides brasiliensis is the leading etiological agent of paracoccidioidomycosis (PCM), a systemic granulomatous disease that typically affects the lungs. Cell wall components of P. brasiliensis interact with host cells and influence the pathogenesis of PCM. In yeast, m...
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ftdoajarticles:oai:doaj.org/article:902c4898e0434f9d88e2de312af742df 2023-05-15T15:14:32+02:00 rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB. Clarissa Xavier Resende Valim Elaine Zayas Marcelino da Silva Mariana Aprigio Assis Fabricio Freitas Fernandes Paulo Sergio Rodrigues Coelho Constance Oliver Maria Célia Jamur 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004032 https://doaj.org/article/902c4898e0434f9d88e2de312af742df EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4552726?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004032 https://doaj.org/article/902c4898e0434f9d88e2de312af742df PLoS Neglected Tropical Diseases, Vol 9, Iss 8, p e0004032 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004032 2022-12-30T23:08:43Z BACKGROUND:The fungus Paracoccidioides brasiliensis is the leading etiological agent of paracoccidioidomycosis (PCM), a systemic granulomatous disease that typically affects the lungs. Cell wall components of P. brasiliensis interact with host cells and influence the pathogenesis of PCM. In yeast, many glycosylphosphatidylinositol (GPI)-anchored proteins are important in the initial contact with the host, mediating host-yeast interactions that culminate with the disease. PbPga1 is a GPI anchored protein located on the surface of the yeast P. brasiliensis that is recognized by sera from PCM patients. METHODOLOGY/PRINCIPAL FINDINGS:Endogenous PbPga1 was localized to the surface of P. brasiliensis yeast cells in the lungs of infected mice using a polyclonal anti-rPbPga1 antibody. Furthermore, macrophages stained with anti-CD38 were associated with P. brasiliensis containing granulomas. Additionally, rPbPga1 activated the transcription factor NFkB in the macrophage cell line Raw 264.7 Luc cells, containing the luciferase gene downstream of the NFkB promoter. After 24 h of incubation with rPbPga1, alveolar macrophages from BALB/c mice were stimulated to release TNF-α, IL-4 and NO. Mast cells, identified by toluidine blue staining, were also associated with P. brasiliensis containing granulomas. Co-culture of P. Brasiliensis yeast cells with RBL-2H3 mast cells induced morphological changes on the surface of the mast cells. Furthermore, RBL-2H3 mast cells were degranulated by P. brasiliensis yeast cells, but not by rPbPga1, as determined by the release of beta-hexosaminidase. However, RBL-2H3 cells activated by rPbPga1 released the inflammatory interleukin IL-6 and also activated the transcription factor NFkB in GFP-reporter mast cells. The transcription factor NFAT was not activated when the mast cells were incubated with rPbPga1. CONCLUSIONS/SIGNIFICANCE:The results indicate that PbPga1 may act as a modulator protein in PCM pathogenesis and serve as a useful target for additional studies on the pathogenesis of P. ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 8 e0004032 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Clarissa Xavier Resende Valim Elaine Zayas Marcelino da Silva Mariana Aprigio Assis Fabricio Freitas Fernandes Paulo Sergio Rodrigues Coelho Constance Oliver Maria Célia Jamur rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:The fungus Paracoccidioides brasiliensis is the leading etiological agent of paracoccidioidomycosis (PCM), a systemic granulomatous disease that typically affects the lungs. Cell wall components of P. brasiliensis interact with host cells and influence the pathogenesis of PCM. In yeast, many glycosylphosphatidylinositol (GPI)-anchored proteins are important in the initial contact with the host, mediating host-yeast interactions that culminate with the disease. PbPga1 is a GPI anchored protein located on the surface of the yeast P. brasiliensis that is recognized by sera from PCM patients. METHODOLOGY/PRINCIPAL FINDINGS:Endogenous PbPga1 was localized to the surface of P. brasiliensis yeast cells in the lungs of infected mice using a polyclonal anti-rPbPga1 antibody. Furthermore, macrophages stained with anti-CD38 were associated with P. brasiliensis containing granulomas. Additionally, rPbPga1 activated the transcription factor NFkB in the macrophage cell line Raw 264.7 Luc cells, containing the luciferase gene downstream of the NFkB promoter. After 24 h of incubation with rPbPga1, alveolar macrophages from BALB/c mice were stimulated to release TNF-α, IL-4 and NO. Mast cells, identified by toluidine blue staining, were also associated with P. brasiliensis containing granulomas. Co-culture of P. Brasiliensis yeast cells with RBL-2H3 mast cells induced morphological changes on the surface of the mast cells. Furthermore, RBL-2H3 mast cells were degranulated by P. brasiliensis yeast cells, but not by rPbPga1, as determined by the release of beta-hexosaminidase. However, RBL-2H3 cells activated by rPbPga1 released the inflammatory interleukin IL-6 and also activated the transcription factor NFkB in GFP-reporter mast cells. The transcription factor NFAT was not activated when the mast cells were incubated with rPbPga1. CONCLUSIONS/SIGNIFICANCE:The results indicate that PbPga1 may act as a modulator protein in PCM pathogenesis and serve as a useful target for additional studies on the pathogenesis of P. ... |
format |
Article in Journal/Newspaper |
author |
Clarissa Xavier Resende Valim Elaine Zayas Marcelino da Silva Mariana Aprigio Assis Fabricio Freitas Fernandes Paulo Sergio Rodrigues Coelho Constance Oliver Maria Célia Jamur |
author_facet |
Clarissa Xavier Resende Valim Elaine Zayas Marcelino da Silva Mariana Aprigio Assis Fabricio Freitas Fernandes Paulo Sergio Rodrigues Coelho Constance Oliver Maria Célia Jamur |
author_sort |
Clarissa Xavier Resende Valim |
title |
rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB. |
title_short |
rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB. |
title_full |
rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB. |
title_fullStr |
rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB. |
title_full_unstemmed |
rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB. |
title_sort |
rpbpga1 from paracoccidioides brasiliensis activates mast cells and macrophages via nfkb. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0004032 https://doaj.org/article/902c4898e0434f9d88e2de312af742df |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 8, p e0004032 (2015) |
op_relation |
http://europepmc.org/articles/PMC4552726?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004032 https://doaj.org/article/902c4898e0434f9d88e2de312af742df |
op_doi |
https://doi.org/10.1371/journal.pntd.0004032 |
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PLOS Neglected Tropical Diseases |
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9 |
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8 |
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e0004032 |
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