Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391973/ https://www.ncbi.nlm.nih.gov/pubmed/28355277 http://dx.doi.org/10.1371/journal.pntd.0005461 |
_version_ | 1783229376389709824 |
---|---|
author | Siqueira, Isaque Medeiros de Castro, Raffael Júnio Araújo Leonhardt, Luiza Chaves de Miranda Jerônimo, Márcio Sousa Soares, Aluízio Carlos Raiol, Tainá Nishibe, Christiane Almeida, Nalvo Tavares, Aldo Henrique Hoffmann, Christian Bocca, Anamelia Lorenzetti |
author_facet | Siqueira, Isaque Medeiros de Castro, Raffael Júnio Araújo Leonhardt, Luiza Chaves de Miranda Jerônimo, Márcio Sousa Soares, Aluízio Carlos Raiol, Tainá Nishibe, Christiane Almeida, Nalvo Tavares, Aldo Henrique Hoffmann, Christian Bocca, Anamelia Lorenzetti |
author_sort | Siqueira, Isaque Medeiros |
collection | PubMed |
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 | Online Article Text |
id | pubmed-5391973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53919732017-05-03 Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity Siqueira, Isaque Medeiros de Castro, Raffael Júnio Araújo Leonhardt, Luiza Chaves de Miranda Jerônimo, Márcio Sousa Soares, Aluízio Carlos Raiol, Tainá Nishibe, Christiane Almeida, Nalvo Tavares, Aldo Henrique Hoffmann, Christian Bocca, Anamelia Lorenzetti PLoS Negl Trop Dis Research Article 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. Public Library of Science 2017-03-29 /pmc/articles/PMC5391973/ /pubmed/28355277 http://dx.doi.org/10.1371/journal.pntd.0005461 Text en © 2017 Siqueira et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Siqueira, Isaque Medeiros de Castro, Raffael Júnio Araújo Leonhardt, Luiza Chaves de Miranda Jerônimo, Márcio Sousa Soares, Aluízio Carlos Raiol, Tainá Nishibe, Christiane Almeida, Nalvo Tavares, Aldo Henrique Hoffmann, Christian Bocca, Anamelia Lorenzetti Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391973/ https://www.ncbi.nlm.nih.gov/pubmed/28355277 http://dx.doi.org/10.1371/journal.pntd.0005461 |
work_keys_str_mv | AT siqueiraisaquemedeiros modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT decastroraffaeljunioaraujo modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT leonhardtluizachavesdemiranda modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT jeronimomarciosousa modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT soaresaluiziocarlos modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT raioltaina modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT nishibechristiane modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT almeidanalvo modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT tavaresaldohenrique modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT hoffmannchristian modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity AT boccaanamelialorenzetti modulationoftheimmuneresponsebyfonsecaeapedrosoimorphotypesinthecourseofexperimentalchromoblastomycosisandtheirroleoninflammatoryresponsechronicity |