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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2019.tde-20032019-162624
Document
Author
Full name
Aline Alves de Lima Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Pagliari, Carla (President)
Andrade, Tânia Sueli de
Criado, Paulo Ricardo
Fernandes, Elaine Raniero
Title in Portuguese
Avaliação imuno-histoquímica de elementos da resposta imune e metaloproteinases em lesões cutâneas verrucosas na cromoblastomicose
Keywords in Portuguese
Células dendríticas
Cromoblastomicose
Fonsecaea nubica
Fonsecaea pedrosoi
Imuno-histoquímica
Macrófagos
Matriz extracelular
Abstract in Portuguese
A cromoblastomicose (CBM) é uma micose crônica cosmopolita muito comum em regiões rurais de países subdesenvolvidos, que compõe o grupo de doenças tropicais negligenciadas. Apesar de seu conhecimento centenário muitas são as questões a serem aclaradas, especialmente do ponto de vista imunológico. Em um estudo transversal retrospectivo, avaliamos por imuno-histoquímica células dendríticas, macrófagos polarizados (M1 e M2) e marcadores de matriz extracelular e os comparamos com espécimes hígidos, além de avaliação intragrupal separando as espécies F. pedrosoi e F. nubica; duas das tantas causadoras de CBM. Os achados evidenciaram participação de CD206+, células CD207/IL-17+, predomínio de macrófagos M2, degradação da matriz extracelular através de alta expressão de MMP-2, MMP-9, Fibronectina e Laminina, entretanto, os níveis de colágeno IV estão preservados. O compilado de dados nos leva a crer que mediante ao invasor as células de Langerhans e CD207/IL-17+ possivelmente se mobilizam para sinalizar a infecção, enquanto macrófagos polarizados contribuem para a captura do patógeno e juntos, células dendríticas e macrófagos, orquestram o estabelecimento da resposta de defesa. Ademais, as incessantes tentativas de contenção da infecção não só não conseguem eliminar o fungo como provocam a degradação da matriz extracelular, contribuindo para a formação de lesões exuberantes e a cronicidade da doença, mantendo tal padrão de resposta quer o patógeno seja a espécie F. pedrosoi quanto a F. nubica. O presente estudo espera contribuir com a melhor compreensão da imunopatologia da CBM e fomentar a discussão sobre opções terapêuticas mais efetivas em um futuro próximo
Title in English
Immunohistochemical evaluation of elements of the immune response and Metalloproteinases in Verrucous skin lesions on Chromoblastomycosis
Keywords in English
Chromoblastomycosis
Dendritic cells
Extracellular matrix
Fonsecaea nubica
Fonsecaea pedrosoi
Immunohistochemistry
Macrophages
Abstract in English
The Chromoblastomycosis (CBM) is a chronic and cosmopolitan mycosis very common to rural regions in underdeveloped countries, which makes up the group of neglected tropical diseases. Despite the centennial discovery of the disease, there are many issues to be clarified, especially from the immunological point of view. We evaluated by immunohistochemistry dendritic cells, polarized macrophages (M1 and M2), markers of extracellular matrix from CBM human skin lesions and compared with healthy specimens. In addition, the group of lesions was compared between F. pedrosoi and F. nubica; two of the many cause of CBM. The findings showed participation of the CD206+, cells co-expressing CD207/IL-17+, predominance of macrophages M2, degradation of the extracellular matrix through the high expression of MMP-2, MMP-9, Fibronectin and Laminin. However, there is preservation of the levels of Collagen IV. The compiled data leads us to believe that, in contact with the invader, Langerhans cells and CD207/IL-17+ cells possibly mobilized to signal infection, while macrophages polarized contribute to the capture of the pathogen and together, dendritic cells and macrophages, orchestrate the establishment of the defense response. Moreover, the incessant attempts to containment of infection not only is unable to eliminate the fungus but also cause the degradation of the extracellular matrix, contributing to the formation of exuberant lesions and the chronicity of the disease, maintaining this pattern of response against both F. pedrosoi or F. nubica. We believe that our study can contribute to the better understanding of the immunopathology of CBM and encourage the discussion on more effective therapeutic options in the near future
 
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Publishing Date
2019-03-22
 
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