Moreira R B, Pirmez C, de Oliveira-Neto M P, Aguiar L S, Gonçalves A J S, Pereira L O R, Abreu L, De Oliveira M P
Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.
Instituto Nacional de Infectologia, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.
Parasite Immunol. 2017 Jul;39(7). doi: 10.1111/pim.12435. Epub 2017 May 29.
The inflammasome is a multiprotein signalling platform involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated gene and protein expression of the inflammasome molecules AIM2 and NLRP3 in active lesions from patients with L. (V.) braziliensis-associated tegumentary leishmaniasis (TL) and correlated these findings with the clinical presentations and responses to therapy. Real-time PCR assays showed a significantly higher AIM2 gene expression in mucosal leishmaniasis (ML) compared with that in cutaneous leishmaniasis (CL). Additionally, AIM2 mRNA expression was significantly higher in lesions from poor responders than in lesions from good responders. In situ protein quantification analyses revealed greater AIM2 expression in ML lesions than in CL lesions. The percentage of AIM2-producing cells was higher in poor responders than in good responders. Although not quite significant, IL-1β+ cells were slightly more prominent in poor responders than in good responders. Similar results were observed when patients were evaluated according to clinical form. GP63 immunostaining was identified in all samples, but no significant variation between mucosal and cutaneous lesions was observed. GP63 could be associated with reduced NLRP3 inflammasome expression in CL and ML patients. Taken together, these data demonstrate that AIM2 is an important component of the inflammasome in TL patients and is directly associated with the severity of lesions.
炎性小体是一种多蛋白信号平台,参与多种炎症性皮肤病的发病机制。在此,我们研究了巴西利什曼原虫(Viannia亚属)相关皮肤利什曼病(TL)患者活动性皮损中炎性小体分子AIM2和NLRP3的基因和蛋白表达,并将这些发现与临床表现及治疗反应相关联。实时PCR分析显示,与皮肤利什曼病(CL)相比,黏膜利什曼病(ML)中AIM2基因表达显著更高。此外,无反应者皮损中的AIM2 mRNA表达显著高于有反应者皮损中的表达。原位蛋白质定量分析显示,ML皮损中的AIM2表达高于CL皮损。产生AIM2的细胞百分比在无反应者中高于有反应者。尽管不太显著,但IL- $1β^+$ 细胞在无反应者中比在有反应者中略为突出。根据临床类型评估患者时也观察到了类似结果。在所有样本中均鉴定出GP63免疫染色,但未观察到黏膜和皮肤病变之间的显著差异。GP63可能与CL和ML患者中NLRP3炎性小体表达降低有关。综上所述,这些数据表明AIM2是TL患者炎性小体的重要组成部分,并且与病变严重程度直接相关。