MIRIAN NACAGAMI SOTTO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
14 resultados
Resultados de Busca
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- Analysis of microvasculature phenotype and endothelial activation markers in skin lesions of lacaziosis (Lobomycosis)(2015) QUARESMA, Juarez A. S.; BRITO, Maysa V.; SOUSA, Jorge R.; SILVA, Luciana M.; HIRAI, Kelly E.; ARAUJO, Rafael S.; BRITO, Arival C. de; CARNEIRO, Francisca R. O.; FUZII, Hellen T.; PAGLIARI, Carla; SOTTO, Mirian N.; DUARTE, Maria I. S.Jorge Lobo's disease is a rare mycosis characterized by chronic inflammation, which causes skin lesions in the absence of visceral dissemination. The disease occurs mainly in hot and humid climates and most cases have been registered in the Brazilian Amazon region. This study investigated possible microvascular alterations in skin lesions caused by infection with Lacazia loboi which may interfere with the clinical progression of the disease. Immunohistochemistry was used to evaluate the density of blood and lymphatic vessels, as well as expression of the cell adhesion molecules ICAM-1, VCAM-1 and E-selectin. The results showed a reduced number of blood (62.66 +/- 20.30 vessels/mm(2)) and lymphatic vessels (3.55 +/- 5.84 vessels/mm(2)) in Jorge Lobo's disease when compared to control skin (169.66 +/- 66.38 blood vessels/mm(2) and 8 +/- 2.17 lymphatic vessels/mm(2)). There were a larger number of vessels expressing ICAM-1 (27.58 +/- 15.32 vessels/mm(2)) and VCAM-1 (7.55 +/- 6.2 vessels/mm(2)). No difference was observed in the expression of E-selectin (4.66 +/- 11 vessels/mm(2)). Taken together, the results indicate changes in the local microvasculature which may interfere with the development of an efficient cell-mediated immune response and may explain restriction of the fungus to the site of injury.
- M2-Polarized Macrophages Determine Human Cutaneous Lesions in Lacaziosis(2020) BARBOZA, Tania Cristina; SOTTO, Mirian Nacagami; KANASHIRO-GALO, Luciane; BRITO, Arival Cardoso de; DUARTE, Maria Irma Seixas; QUARESMA, Juarez Antonio Simoes; PAGLIARI, CarlaLacaziosis is a cutaneous chronic mycosis caused by Lacazia loboi. Macrophages are important cells in the host immune response in fungal infections. The macrophage population exhibits strong plasticity that varies according to the stimuli in the microenvironment of lesions M1 profile promotes a Th1 pattern of cytokines and a microbicidal function and M2 is related to Th2 cytokines and immunomodulatory response. We investigated the population of M1 and M2 polarized macrophages in human cutaneous lesions. A total of 27 biopsies from human lesions were submitted to an immunohistochemistry protocol using antibodies to detect M1 and M2 macrophages (Arginase-1, CD163, iNOS, RBP-J and cMAF). We could observe high number of cells expressing Arginase1, CD163 and c-MAF that correspond to elements of the M2 profile of macrophage, over iNOS and RBP-J (elements of the M1 profile). The results suggest a predominant phenotype of M2 macrophages, which have an immunomodulatory role and probably contributing to chronicity of Lacaziosis.
- The cytotoxic T cells may contribute to the in situ immune response in Jorge Lobo's Disease human lesions(2017) ALEXANDRE, Ariane Fernandes; QUARESMA, Juarez Antonio Simoes; BARBOZA, Tania Cristina; BRITO, Arival Cardoso de; XAVIER, Marilia Brasil; OLIVEIRA, Clivia Maria Moraes de; UNGER, Deborah Aben Athar; KANASHIRO-GALO, Luciane; SOTTO, Mirian Nacagami; DUARTE, Maria Irma Seixas; PAGLIARI, CarlaJorge Lobo's Disease (JLD) is a cutaneous chronic granulomatous disease caused by the pathogenic fungus Lacazia loboi. It is characterized by a granulomatous reaction with multinucleated giant cells and high number of fungal cells. In order to contribute to the comprehension of immune mechanisms in JLD human lesions, we studied the cytotoxic immune response, focusing on TCD8+ and NK cells, and granzyme B. Forty skin biopsies of lower limbs were selected and an immunohistochemistry protocol was developed to detect CD8+ T cells, NK cells and Granzyme B. In order to compare the cellular populations, we also performed a protocol to visualize TCD4+ cells. Immunolabeled cells were quantified in nine randomized fields in the dermis. Lesions were characterized by inflammatory infiltrate of macrophages, lymphocytes, epithelioid and multinucleated giant cells with intense number of fungal forms. There was a prevalence of CD8 over CD4 cells, followed by NK cells. Our results suggest that in JLD the cytotoxic immune response could represent another important mechanism to control Lacazia loboi infection. We may suggest that, although CD4+ T cells are essential for host defense in JLD, CD8+ T cells could play a role in the elimination of the fungus.
- Revisiting Langerhans cells in paracoccidioidomycosis: expression of CD207/langerin in human cutaneous and mucosal lesions(2011) PAGLIARI, Carla; FERNANDES, Elaine Raniero; SILVA, Wellington Luiz Ferreira da; SILVA, Aline Alves de Lima; STEGUN, Felipe Weisshaupt; DUARTE, Maria Irma Seixas; SOTTO, Mirian NacagamiLangerhans cells are identified by the expression of langerin. We detected this molecule in cutaneous and mucosal lesions in paracoccidioidomycosis, an important infection in Latin America. Langerin+ cells were scarcely distributed, with short dendrites in epidermis and epithelium and were frequent in the dermis and corium, in the inflammatory infiltrate and granulomas. Mucosal lesions presented a higher expression of langerin in lesions with loose granulomas. For the first time we presented the expression of langerin in paracoccidioidomycosis. Positive cells in dermis and corium could represent migrating Langerhans cells or a new subset of langerin+ cells with a role in paracoccidioidomycosis.
- Th17 and regulatory T cells contribute to the in situ immune response in skin lesions of Jorge Lobo's disease(2016) KANASHIRO-GALO, Luciane; PAGLIARI, Carla; BARBOZA, Tania Cristina; BRITO, Arival Cardoso de; XAVIER, Marilia Brasil; OLIVEIRA, Clivia Maria Moraes de; UNGER, Deborah Aben Athar; SOTTO, Mirian Nacagami; QUARESMA, Juarez Antonio Simoes; DUARTE, Maria Irma SeixasJorge Lobo's disease (JLD) is a chronic granulomatous mycosis described in various Latin American countries. The main objective of the present study was to investigate the possible role of Th17 and Foxp3+ Treg cells in the pathogenesis of Jorge Lobo's disease. Human skin biopsies were submitted to an immunohistochemistry protocol to detect Foxp3, interleukin (IL)-1beta, CD25, IL-6, IL-17, and IL-23. The epidermis presented acanthosis, hyperkeratosis, and frequent presence of fungi. The dermis presented inflammatory infiltrate comprising macrophages, lymphocytes, epithelioid and multinucleated cells, and an intense number of fungi. Foxp3+ Treg cells and IL-17+ cells were visualized in lymphocytes in the inflammatory infiltrate. IL-1, IL-2R (CD25), IL-6, and IL-23 were visualized in the dermis, intermingled with fungal cells, permeating or participating of the granuloma. Following IL-17, the most prominent cytokine was IL-6. IL-23 and cells expressing CD25 were present in fewer number. The comparative analysis between IL-17 and Foxp3 demonstrated a statistically significant increased number of IL-17+ cells. Th17 cells play a role in the immune response of JLD. IL-1beta and IL-6 added to the previously described increased number of TGF-beta would stimulate such pattern of response. Th17 cells could be present as an effort to modulate the local immune response; however, high levels of a Th17 profile could overcome the role of Treg cells. The unbalance between Treg/Th17 cells seems to corroborate with the less effective immune response against the fungus.
- Jorge Lobo's Disease: Immunohistochemical Characterization of Dendritic Cells in Cutaneous Lesions(2015) BARBOZA, Tania Cristina; QUARESMA, Juarez Antonio Simoes; BRITO, Arival Cardoso de; XAVIER, Marilia Brasil; OLIVEIRA, Clivia Maria Moraes de; UNGER, Deborah Aben Athar; DUARTE, Maria Irma Seixas; SOTTO, Mirian Nacagami; PAGLIARI, CarlaJorge Lobo's disease (JLD) is a cutaneous chronic mycosis caused by Lacazia loboi. We studied Factor XIIIa + dermal dendrocytes (FXIIIa + DD), Langerhans cells (LC) through the expression of langerin and the expression of S100 protein. A total of 41 biopsies and 10 normal skins (control) were developed with a polymer-based immunohistochemical method. Lesions presented infiltrate comprising macrophages, some asteroid corpuscles, lymphocytes, multinucleated giant cells and a large number of fungi. LCs presented short dendrites and were scarcely distributed. Dermal langerin + cells were detected in nine JLD lesions. FXIIIa + DD were hypertrophic, visualized in the inflammatory infiltrate of JLD lesions. Cells S100+ were present in JLD and control group with a similar number of cells. A total of 14 specimens did not express FXIIIa, and this considerable number probably contributed to the statistical similarity with the control group. The results indicate that LCs are present in the immune response against Lacazia loboi. Some dermal langerin + cells could be another subset of dendritic cells. Our data indicate changes of LCs in JLD cutaneous lesions and present, for the first time, results that show langerin + cells in the dermis and corroborate previous observations on the participation of FXIIIa + DD in the in situ immune response in JLD.
conferenceObject Histopathological Aspects of Acute-Form Paracoccidioidomycosis in IL-12BR1 Deficient Patients(2014) VASCONCELOS, D. Moraes; CAMPEAS, A. E.; FERRAO, M. S.; YU, C. L.; PAGLIARI, C.; BRASIL, R. A.; SOTTO, M. N.; DUARTE, M. I. S.- Regulatory T cells in cutaneous lesions of patients with Paracoccidioidomycosis(2013) SILVA, Aline Alves de Lima; SOTTO, Mirian N.; DUARTE, Maria Irma Seixas; PAGLIARI, CarlaParacoccidioidomycosis (PCM) is a systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis, with high incidence in Brazil and very significant in Latin America. The disease is clinically classified as acute, subacute or chronic where the primary lesion initiates in the lungs and can spread to other organs such as the skin and mucous membranes. The lesions are characterized by granulomatous formation, organized according to the type of pattern of host immune response. We demonstrated and quantified by immunohistochemistry the expression of Foxp3, CD25, TGF-beta and IL-10 in thirty cutaneous lesions with different presentation of granulomatous response. Cells expressing Foxp3 and CD25 were increased in lesions with compact granulomas. The expression of TGF-beta and IL-10 was similar in all PCM lesions. As previous studies, our data suggest the correlation of Treg cells with the chronicity of the disease and the participation in suppressing mechanism as a possible source of IL-10. TGF-beta and IL-10, two important suppressor cytokines, are expressed in great amounts in the lesions but our results do not allow correlating with the differences in the granulomatous response.
- Paracoccidioides brasiliensis interacts with dermal dendritic cells and keratinocytes in human skin and oral mucosa lesions(2016) SILVA, Wellington Luiz Ferreira da; PAGLIARI, Carla; DUARTE, Maria Irma Seixas; SOTTO, Mirian N.Paracoccidioidomycosis (PCM) is a systemic disease caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. In PCM the skin and oral mucosa are often affected. Dendritic cells and keratinocytes of the integument play a role in innate and adaptive immune response against pathogens, due to their function as antigen presenting cells. Aiming to verify the interaction of P. brasiliensis with these cell populations, we studied 52 skin and 47 oral mucosa samples taken from patients with proven diagnosis of PCM. The biopsies were subjected to immunohistochemical and/or immunofluorescence staining with anti-factor XIIIa (marker of dermal dendrocytes), anti-CD207 (marker ofmature Langerhans cells), anti-pan cytokeratins (AE1-AE3) and anti-P. brasiliensis antibodies. Analyses with confocal laser microscopy were also performed for better visualization of the interaction between keratinocytes and the fungi. In sum, 42% of oral mucosa samples displayed yeast forms in Factor XIIIa dermal dendrocytes cytoplasm. Langerhans cells in skin and oral mucosa samples did not show yeast cells in their cytoplasm. In sum, 54% of skin and 60% of mucosal samples displayed yeast cells in the cytoplasm of keratinocytes. The parasitism of keratinocytes may represent a possible mechanism of evasion of the fungus to local immune mechanisms. Factor XIIIa dendrocytes and keratinocytes may be acting as antigen-presenting cells to fulfill the probably impaired function of Langerhans cells in skin and oral mucosa of human PCM.
- Paracoccidioidomycosis: Cells expressing IL17 and Foxp3 in cutaneous and mucosal lesions(2011) PAGLIARI, Carla; FERNANDES, Elaine Raniero; STEGUN, Felipe Weisshaupt; SILVA, Wellington Luiz F. da; DUARTE, Maria Irma Seixas; SOTTO, Mirian N.We demonstrated and quantified by immunohistochemistry the population of cells expressing IL17 and Foxp3 in cutaneous and mucosal paracoccidioidomycosis lesions, associating these populations of cells with different presentations of granulomatous response. For this purpose, 61 skin biopsies and 55 oral mucosal biopsies were evaluated. Cells expressing IL17 were distributed in the inflammatory infiltrate in both groups of lesions and were found in the vessels' wall too. Foxp3+ expression was limited to the nuclei of lymphocytes in the inflammatory infiltrate. The distribution of IL17 was similar among the groups; however, Foxp3+ cells were increased in mucosal lesions that displayed compact granulomas. The results suggest that IL17 seems to play a role in paracoccidioidomycosis cutaneous and mucosal lesions, probably as secondary cells in the clearance of the fungal antigens. The presence of Foxp3+ cells both in skin and mucosa corroborates some previous researches that suggest the role of this group of cells in the modulation of local immune response.