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MODULATION OF THE IMMUNE RESPONSE BY FONSECAEA PEDROSOI MORPHOTYPES IN THE COURSE OF EXPERIMENTAL CHROMOBLASTOMYCOSIS AND THEIR ROLE ON INFLAMMATORY RESPONSE CHRONICITY
Fungal diseases
Gene expression
Inflammation
Inflammatory diseases
Cytokines
Fungal genetics
Phagocytosis
Ascomicetos
Cromoblastomicose
Citocinas
Modelos Animais de Doenças
Sequenciamento de Nucleotídeos em Larga Escala
Hifas
Lectinas Tipo C
Macrófagos
Camundongos Endogâmicos BALB C
Fagocitose
Análise de Sequência de RNA
Interações Hospedeiro-Patógeno
Esporos Fúngicos
Autor
Afiliación
University of Brasília. School of Medicine. Molecular Pathology Post-Graduate Program. Brasília, DF, Brazil.
University of Brasília. School of Medicine. Molecular Pathology Post-Graduate Program. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
University of Brasília. University Hospital. Brasília, DF, Brazil.
Fundação Oswaldo Cruz. Fiocruz Amazonas. Instituto Leônidas e Maria Deane Manaus, AM, Brasil.
Federal University of Mato Grosso do Sul. School of Computing Sciences. Campo Grande, MS, Brazil.
Federal University of Mato Grosso do Sul. School of Computing Sciences. Campo Grande, MS, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil / University of São Paulo. School of Pharmaceutical Sciences. Department of Food Sciences and Experimental Nutrition, São Paulo, SP, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
University of Brasília. School of Medicine. Molecular Pathology Post-Graduate Program. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
University of Brasília. University Hospital. Brasília, DF, Brazil.
Fundação Oswaldo Cruz. Fiocruz Amazonas. Instituto Leônidas e Maria Deane Manaus, AM, Brasil.
Federal University of Mato Grosso do Sul. School of Computing Sciences. Campo Grande, MS, Brazil.
Federal University of Mato Grosso do Sul. School of Computing Sciences. Campo Grande, MS, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil / University of São Paulo. School of Pharmaceutical Sciences. Department of Food Sciences and Experimental Nutrition, São Paulo, SP, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Brasília, DF, Brazil.
Resumen en ingles
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.
Palabras clave en ingles
MacrophagesFungal diseases
Gene expression
Inflammation
Inflammatory diseases
Cytokines
Fungal genetics
Phagocytosis
DeCS
ApoptoseAscomicetos
Cromoblastomicose
Citocinas
Modelos Animais de Doenças
Sequenciamento de Nucleotídeos em Larga Escala
Hifas
Lectinas Tipo C
Macrófagos
Camundongos Endogâmicos BALB C
Fagocitose
Análise de Sequência de RNA
Interações Hospedeiro-Patógeno
Esporos Fúngicos
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