MARIA IRMA SEIXAS DUARTE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina - Líder
5 resultados
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- Dengue fever ophthalmic manifestations: A review and update(2023) LUCENA-NETO, Francisco Dias; FALCAO, Luiz Fabio Magno; MORAES, Evelly Christinne da Silva; DAVID, Joacy Pedro Franco; VIEIRA-JUNIOR, Adolfo de Souza; SILVA, Camilla Costa; SOUSA, Jorge Rodrigues de; DUARTE, Maria Irma Seixas; VASCONCELOS, Pedro Fernando da Costa; QUARESMA, Juarez Antonio SimoesDengue fever, the most common arbovirus disease, affects an estimated 390 million people annually. Dengue virus (DENV) is an RNA virus of the Flaviviridae family with four different serotypes. Dengue haemorrhagic fever is the deadliest form of dengue infection and is characterised by thrombocytopaenia, hypotension, and the possibility of multi-system organ failure. The mechanism hypothesised for DENV viral replication is intrinsic antibody-dependent enhancement, which refers to Fc gamma receptor-mediated viral amplification. This hypothesis suggests that the internalisation of DENV through the Fc gamma receptor inhibits antiviral genes by suppressing type-1 interferon-mediated antiviral responses. DENV NS1 antibodies can promote the release of various inflammatory mediators in the nuclear transcription factor pathway (NF-kappa B-dependent), including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-8. As a result, MCP-1 increases ICAM-1 expression and facilitates leukocyte transmigration. In addition, anti-DENV NS1 antibodies induce endothelial cell apoptosis via a nitric oxide-regulated pathway. A chain reaction involving pre-existing DENV heterotypic antibodies and innate immune cells causes dysfunction in complement system activity and contributes to the action of autoantibodies and anti-endothelial cells, resulting in endothelial cell dysfunction, blood-retinal barrier breakdown, haemorrhage, and plasma leakage. A spectrum of ocular diseases associated with DENV infection, ranging from haemorrhagic to inflammatory manifestations, has been reported in the literature. Although rare, ophthalmic manifestations can occur in both the anterior and posterior segments and are usually associated with thrombocytopenia. The most common ocular complication is haemorrhage. However, ophthalmic complications, such as anterior uveitis and vasculitis, suggest an immune-mediated pathogenesis.
- Plasmacytoid Dendritic Cells, the Expression of the Stimulator of Interferon Genes Protein (STING) and a Possible Role of Th17 Immune Response in Cervical Lesions Mediated by Human Papillomavirus(2023) JESUS, Ana Carolina Caetano; MENICONI, Maria Cristina Goncalves; GALO, Luciane Kanashiro; DUARTE, Maria Irma Seixas; SOTTO, Mirian Nacagami; PAGLIARI, CarlaHuman papillomavirus (HPV) is a virus with a DNA structure that specifically targets squamous epithelial cells. In individuals with a healthy immune system, HPV infection is typically resolved naturally, leading to spontaneous regression. However, when the viral genetic material integrates into the host DNA, it can disrupt the immune response and eventually give rise to neoplastic manifestations. Remarkably, HPV infection appears to activate a protein called Stimulator of Interferon genes (STING), which contributes to the infiltration of Treg Foxp3 + cells. This cellular response acts as a predisposing factor in patients with HPV, potentially exacerbating the progression of the infection. The STING is versatile in different circumstances and can play a role in the immune response as an anti-tumour therapeutic target in HPV-related carcinogenesis. The function of Th17 cells is ambiguous, depending on the microenvironment in the tumour. In this study, 46 biopsies of the uterine cervix of human immunodeficiency virus (HIV) positive patients were divided into three groups: I-cervicitis (10); II-low-grade intraepithelial neoplasia (26); III-moderate or severe intraepithelial neoplasia (10) and it was performed an immunohistochemical technique with the specific antibodies to HPV, CD123, STING and IL17. Immunostained cells were quantified and statistically analysed. Antigens of HPV were detected in the cervical intraepithelial neoplasia (CIN) groups and were absent in cervicitis group. The expression of CD123 was positive in 10.87% of the casuistic, with no statistical difference among groups. STING was present in the three groups. Group 1 presented an area fraction that varied from 3 to 20%, group 2 presented a variation of 3-23% and group 3 presented an area fraction between 4 and 12%. Cells expressing IL17 were present in three groups, more frequent in cervicitis. Considering that the casuistic is composed of women carrying HIV, this infectious agent could influence the numerical similarities of the cells studied among three groups, even in the absence of HPV. Stimulator of Interferon genes protein (STING) is versatile in different mechanisms in the immune response and may be a target in HPV-related carcinogenesis. Through immunohistochemistry it was detected IL17 in cervicitis and lesions with HPV. Also, CD123 + plasmacytoid cells seems to play a role both in cervicitis and lesions mediated by HPV.
- Comparative Analysis of Human Hepatic Lesions in Dengue, Yellow Fever, and Chikungunya: Revisiting Histopathological Changes in the Light of Modern Knowledge of Cell Pathology(2023) RIBEIRO, Yasmin Pacheco; FALCAO, Luiz Fabio Magno; SMITH, Vanessa Cavaleiro; SOUSA, Jorge Rodrigues de; PAGLIARI, Carla; FRANCO, Edna Cristina Santos; CRUZ, Ana Cecilia Ribeiro; CHIANG, Janniffer Oliveira; MARTINS, Livia Caricio; NUNES, Juliana Abreu Lima; VILACOERT, Fellipe Souza da Silva; SANTOS, Lais Carneiro dos; FURLANETO, Matheus Perini; FUZII, Hellen Thais; FILHO, Marcos Virgilio Bertonsin; COSTA, Luccas Delgado da; DUARTE, Maria Irma Seixas; FURLANETO, Ismari Perini; FILHO, Arnaldo Jorge Martins; AARAO, Tinara Leila de Souza; VASCONCELOS, Pedro Fernando da Costa; QUARESMA, Juarez Antonio SimoesArboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.
- Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions(2023) QUARESMA, Tatiane Costa; VALENTIM, Livia de Aguiar; SOUSA, Jorge Rodrigues de; AARAO, Tinara Leila de Souza; FUZII, Hellen Thais; DUARTE, Maria Irma Seixas; SOUZA, Juarez de; QUARESMA, Juarez Antonio SimoesMycobacterium leprae is the etiological agent of leprosy. Macrophages (M phi s) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of M phi subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-na & iuml;ve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Par & aacute;, Bel & eacute;m, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-alpha) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-beta, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-alpha e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 +/- 1.3, p < 0.0001), Borderline (1.6 +/- 0.4, p < 0.0001), and tuberculoid (TT) (12.5 +/- 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 +/- 2.3, p < 0.0001), Borderline (1.3 +/- 0.2, p < 0.0001), and TT (3.2 +/- 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 +/- 1.7, p < 0.0001), Borderline (1.2 +/- 0.2, p < 0.0001), and TT (2.6 +/- 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 x TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 M phi s constituted the predominant M phi subpopulation in the TT and Borderline forms of leprosy, whereas the M2 M phi s showed increased immunoexpression and M4 was the predominant M phi phenotype in VV leprosy. These results confirm the relationship of the M phi profile with chronic pathological processes of the inflammatory response in leprosy.
- Monkeypox Virus Immune Evasion and Eye Manifestation: Beyond Eyelid Implications(2023) LUCENA-NETO, Francisco D.; FALCAO, Luiz F. M.; VIEIRA-JUNIOR, Adolfo S.; MORAES, Evelly C. S.; DAVID, Joacy P. F.; SILVA, Camilla C.; SOUSA, Jorge R.; DUARTE, Maria I. S.; VASCONCELOS, Pedro F. C.; QUARESMA, Juarez A. S.Monkeypox virus (MPXV), belonging to the Poxviridae family and Orthopoxvirus genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFN gamma, CC and CXC chemokines, IL-1 beta, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFN alpha and IFN beta. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.