RESUMO
The host defense mechanism in chromoblastomycosis has not been thoroughly investigated. It has been suggested that cell-mediated immunity in patients with long-standing chromoblastomycosis is somehow impaired. As a result, these individuals became unable to develop an efficient immune reaction. Many studies have shown that monocyte-derived macrophages exhibit critical activities in immunity to microorganisms. Moreover, the ability of cells from the monocytic lineage to process and present antigens, to produce cytokines, and to provide costimulatory signals confirms their pivotal role in the initiation of specific immune responses. In the present study, it was observed that monocytes from patients with a severe form of disease had a higher production of IL-10 and a lower expression of HLA-DR and costimulatory molecules when stimulated with specific antigen or LPS. Immune modulation with recombinant IL-12 or anti-IL-10 can restore the antigen-specific Th1-type immune response in chromoblastomycosis patients by up-regulating HLA-DR and costimulatory molecules in monocytes. Therefore, our data show that monocytes from patients with different clinical forms of chromoblastomycosis present distinct phenotypic and functional profiles. This observation suggests possible mechanisms that control the T cell response and influence their role in the development of pathology.
Assuntos
Ascomicetos/isolamento & purificação , Cromoblastomicose/imunologia , Cromoblastomicose/metabolismo , Citocinas/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Ascomicetos/patogenicidade , Antígeno B7-1/imunologia , Antígeno B7-1/metabolismo , Antígeno CTLA-4 , Comunicação Celular/imunologia , Proliferação de Células , Cromoblastomicose/microbiologia , Citocinas/imunologia , Feminino , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Humanos , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-12/imunologia , Interleucina-12/metabolismo , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/microbiologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/microbiologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Chromoblastomycosis is characterized by the slow development of polymorphic skin lesions (nodules, verrucas, tumores, plaques and scar tissue). Inside the host, infectious propagules adhere to epithelial cells and differentiate into sclerotic forms, which effectively resist destruction by host effector cells and allow onset of chronic disease. A cellular immune response against fungi is essential to control infection. Amongst the cells of the immune system, macrophages play the most important role in controlling fungal growth. In this study, we show that the fungicidal characteristic of macrophages is dependent on the fungal species that causes chromoblastomycosis. We began by observing that the phagocytic index was higher for Fonsecaea pedrosoi and Rhinocladiella aquaspersa compared with that of other fungi. Complement-mediated phagocytosis was more important for Phialophora verrucosa and R. aquaspersa and was inhibited by mannan when F. pedrosoi and R. aquaspersa conidia were phagocytosed by macrophages. We showed that macrophages killed significantly only R. aquaspersa. We also found that the phagocytosis of fungi has functional consequences for macrophages as phagocytosis resulted in down-modulation of MHC-II and CD80 expression as well as in the inhibition of the basal liberation of NO. However, the inhibition of the basal liberation of NO nor the down-modulation of MHC and co-stimulatory molecules were observed in the presence of R. aquaspersa.