Title:	Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity
Authors:	Siqueira, Isaque Medeiros Castro, Raffael Júnio Araújo de Leonhardt, Luiza Chaves de Miranda Jerônimo, Márcio Sousa Soares, Aluízio Carlos Raiol, Tainá Nishibe, Christiane Almeida, Nalvo Tavares, Aldo Henrique Fonseca Pacheco Hoffmann, Christian Bocca, Anamélia Lorenzetti
Assunto::	Inflamação Micoses Fungos - doenças Células
Issue Date:	29-Mar-2017
Publisher:	Plos One
Citation:	SIQUEIRA, Isaque Medeiros. et al. Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity. Plos One Neglected Tropical Diseases, v. 11, n. 3, Article e0005461, 29 mar. 2017. Disponível em: <http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005461>. Acesso em: 9 jun. 2017. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005461.
Abstract:	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. Highthroughput 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.
Licença::	© 2017 Siqueira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI:	https://dx.doi.org/10.1371/journal.pntd.0005461
Appears in Collections:	Artigos publicados em periódicos e afins

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