Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity.
A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chr...
Published in: | PLOS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:a0c719b8bdaf4932a5f0f69279af272d 2023-05-15T15:11:47+02:00 Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. Isaque Medeiros Siqueira Raffael Júnio Araújo de Castro Luiza Chaves de Miranda Leonhardt Márcio Sousa Jerônimo Aluízio Carlos Soares Tainá Raiol Christiane Nishibe Nalvo Almeida Aldo Henrique Tavares Christian Hoffmann Anamelia Lorenzetti Bocca 2017-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005461 https://doaj.org/article/a0c719b8bdaf4932a5f0f69279af272d EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5391973?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005461 https://doaj.org/article/a0c719b8bdaf4932a5f0f69279af272d PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005461 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005461 2022-12-31T05:33:52Z A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM), a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq) performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 3 e0005461 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Isaque Medeiros Siqueira Raffael Júnio Araújo de Castro Luiza Chaves de Miranda Leonhardt Márcio Sousa Jerônimo Aluízio Carlos Soares Tainá Raiol Christiane Nishibe Nalvo Almeida Aldo Henrique Tavares Christian Hoffmann Anamelia Lorenzetti Bocca Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM), a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq) performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections. |
format |
Article in Journal/Newspaper |
author |
Isaque Medeiros Siqueira Raffael Júnio Araújo de Castro Luiza Chaves de Miranda Leonhardt Márcio Sousa Jerônimo Aluízio Carlos Soares Tainá Raiol Christiane Nishibe Nalvo Almeida Aldo Henrique Tavares Christian Hoffmann Anamelia Lorenzetti Bocca |
author_facet |
Isaque Medeiros Siqueira Raffael Júnio Araújo de Castro Luiza Chaves de Miranda Leonhardt Márcio Sousa Jerônimo Aluízio Carlos Soares Tainá Raiol Christiane Nishibe Nalvo Almeida Aldo Henrique Tavares Christian Hoffmann Anamelia Lorenzetti Bocca |
author_sort |
Isaque Medeiros Siqueira |
title |
Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. |
title_short |
Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. |
title_full |
Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. |
title_fullStr |
Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. |
title_full_unstemmed |
Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. |
title_sort |
modulation of the immune response by fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005461 https://doaj.org/article/a0c719b8bdaf4932a5f0f69279af272d |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005461 (2017) |
op_relation |
http://europepmc.org/articles/PMC5391973?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005461 https://doaj.org/article/a0c719b8bdaf4932a5f0f69279af272d |
op_doi |
https://doi.org/10.1371/journal.pntd.0005461 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
3 |
container_start_page |
e0005461 |
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1766342589898817536 |