Araújo Vera Cavalcanti, Demasi Ana Paula Dias, Soares Andresa Borges, Passador-Santos Fabrício, Napimoga Marcelo Henrique, Martinez Elizabeth Ferreira, Freitas Nadir Severina, Araújo Ney Soares
Department of Pathology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo, Brazil.
PLoS One. 2013 Oct 24;8(10):e76976. doi: 10.1371/journal.pone.0076976. eCollection 2013.
Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM), as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.
除了其主要的吞噬和病原体破坏作用外,中性粒细胞还与几种传染病中的肉芽肿形成有关。已经证明,Nrf2调节中性粒细胞中的抗氧化保护作用,在不损害宿主细菌防御能力的情况下减轻炎症。在本研究中,我们分析了巴西副球孢子菌病(PCM)中中性粒细胞的存在情况以及Nrf2的免疫表达。根据真菌数量以及松散或组织良好的肉芽肿和微脓肿的存在情况,对39例口腔PCM病例进行了分类。使用Nrf2抗体进行免疫组织化学分析。结果显示,中性粒细胞存在于微脓肿和松散的肉芽肿中,但在结构良好的肉芽肿中不存在。与松散和组织良好的肉芽肿相比,仅存在松散肉芽肿的病例中显示出更多的真菌。在松散肉芽肿和脓肿的中性粒细胞细胞核中观察到Nrf2,尽管同一标本中还存在组织良好的肉芽肿,但它在松散肉芽肿中的表达仍然维持。本研究表明,中性粒细胞参与巴西副球孢子菌肉芽肿的形成,并且Nrf2可能通过调节炎症反应在中性粒细胞存活中发挥作用。