Abstract：
BACKGROUND: Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, with a high incidence in Brazil, Colombia and Venezuela, and constitutes a serious public health problem, a frequent cause of morbidity and disability for work. Some mechanisms of cell death are described as important tools in infectious processes. When apoptosis is blocked, RIPK (Receptor-interacting protein kinase) 3 dependent, a caspase-independent form of cell death, can limit the replication and spread of pathogens. Some molecules that mediate necroptosis include RIPK3 and have been extensively studied due to their signalling mechanism and pathological function. RIPK3 activates NLRP1 and NLRP3-mediated inflammasome formation. Caspase-1 has an important role in processing the cytokines ILβ and IL18 to their active form. Such molecules are part of the inflammasome characterization, whose caspase-1-dependent activation promotes the death of pyroptotic cells and the secretion of proinflammatory cytokines. Knowledge about the mechanisms of pathogen-mediated cell death can be useful for understanding of the pathogenesis of infections and inflammatory conditions.
OBJECTIVE: The objective of this work was to identify the mechanisms of programmed cell death and inflammasome components in human oral mucosal lesions of paracoccidioidomycosis through immunohistochemical methods and identification of RIPK-3, IL1β, IL18, NLRP-1 and caspase-1. Thirty specimens were included, and a histopathological analysis of the lesions was performed using haematoxylin-eosin staining.
RESULTS: Our results on in situ expression of inflammasome elements and programmed cell death showed increased expression of IL-1β, NLRP-1, caspase-1 and RIPK-3. We suggest that inflammasome complex participate in the immunopathogenesis in paracoccidioidomycosis oral lesions in an interplay with RIPK3.
OBJECTIVE: The objective of this work was to identify the mechanisms of programmed cell death and inflammasome components in human oral mucosal lesions of paracoccidioidomycosis through immunohistochemical methods and identification of RIPK-3, IL1β, IL18, NLRP-1 and caspase-1. Thirty specimens were included, and a histopathological analysis of the lesions was performed using haematoxylin-eosin staining.
RESULTS: Our results on in situ expression of inflammasome elements and programmed cell death showed increased expression of IL-1β, NLRP-1, caspase-1 and RIPK-3. We suggest that inflammasome complex participate in the immunopathogenesis in paracoccidioidomycosis oral lesions in an interplay with RIPK3.
摘要：
背景：副孢子菌病是拉丁美洲最普遍的全身性真菌病，在巴西发病率很高，哥伦比亚和委内瑞拉,并构成严重的公共卫生问题，工作中常见的发病和残疾原因。细胞死亡的一些机制被描述为感染过程中的重要工具。当细胞凋亡被阻断时，RIPK（受体相互作用蛋白激酶）3依赖性，一种不依赖caspase的细胞死亡形式，可以限制病原体的复制和传播。一些介导坏死性凋亡的分子包括RIPK3,并且由于其信号传导机制和病理功能而被广泛研究。RIPK3激活NLRP1和NLRP3介导的炎性小体形成。Caspase-1在将细胞因子ILβ和IL18加工成它们的活性形式中具有重要作用。这些分子是炎症小体表征的一部分，其依赖caspase-1的激活促进了焦化细胞的死亡和促炎细胞因子的分泌。了解病原体介导的细胞死亡机制有助于了解感染和炎症的发病机理。
目的：这项工作的目的是通过免疫组织化学方法和RIPK-3，IL1β的鉴定，确定人副角菌病口腔粘膜病变中程序性细胞死亡和炎症体成分的机制。IL18、NLRP-1和胱天蛋白酶-1。包括30个标本，使用苏木精-伊红染色对病变进行组织病理学分析。
结果：我们关于炎症小体元件的原位表达和程序性细胞死亡的结果显示IL-1β的表达增加，NLRP-1、胱天蛋白酶-1和RIPK-3。我们建议炎性体复合物与RIPK3相互作用，参与副角菌病口腔病变的免疫发病机制。
目的：这项工作的目的是通过免疫组织化学方法和RIPK-3，IL1β的鉴定，确定人副角菌病口腔粘膜病变中程序性细胞死亡和炎症体成分的机制。IL18、NLRP-1和胱天蛋白酶-1。包括30个标本，使用苏木精-伊红染色对病变进行组织病理学分析。
结果：我们关于炎症小体元件的原位表达和程序性细胞死亡的结果显示IL-1β的表达增加，NLRP-1、胱天蛋白酶-1和RIPK-3。我们建议炎性体复合物与RIPK3相互作用，参与副角菌病口腔病变的免疫发病机制。
