Souza de Lima D, Ogusku M M, Sadahiro A, Pontillo A
Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil; Laboratório Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM, Brazil.
Laboratório de Micobacteriologia, Institut oNacional de Pesquisas da Amazônia, Manaus, AM, Brazil.
Infect Genet Evol. 2016 Jul;41:240-244. doi: 10.1016/j.meegid.2016.04.015. Epub 2016 Apr 19.
Tuberculosis (TB) continues to be a major public health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb) but remains asymptomatic (latent TB) and only 5% to 10% of these latent individuals will develop active pulmonary TB. Factors affecting the balance between latent and active TB are mostly unknown, even if host genome has been shown to contribute to the outcome of Mtb response. Acute inflammation and Th1 response are important in the early clearance of the bacteria as it was emphasized by the association between immune genes (i.e.: HLA, IFNG, TNF, NRPAM1, IL10) variants and the development of active pulmonary TB. Recently, the role of the inflammasome in experimental TB has been demonstrated, however, to our knowledge, no data still exist about the contribution of inflammasome genetics to Mtb susceptibility and/or to the development of active TB. For this reason, selected polymorphisms in inflammasome genes were analysed in a case/control cohort of individuals with active pulmonary TB from an endemic area of Brazil Amazon. Our data evidence the novel association between polymorphisms in NLRP3-inflammasome encoding genes and active pulmonary TB, and replicated the association between P2X7 and TB observed in other populations. These results emphasize the role of NLRP3-inflammasome also in human TB, and contribute to our knowledge about pathways involved in the development of active TB, even if deeper investigation are needed to fully elucidate the role of the complex in Mtb infection.
结核病（TB）仍然是一个重大的公共卫生问题。据估计，全球三分之一的人口感染了结核分枝杆菌（Mtb），但仍无症状（潜伏性结核），这些潜伏感染者中只有5%至10%会发展为活动性肺结核。影响潜伏性结核和活动性结核之间平衡的因素大多未知，尽管宿主基因组已被证明对Mtb反应的结果有影响。急性炎症和Th1反应在细菌的早期清除中很重要，这一点通过免疫基因（即：HLA、IFNG、TNF、NRPAM1、IL10）变体与活动性肺结核的发展之间的关联得到了强调。最近，炎症小体在实验性结核病中的作用已得到证实，然而，据我们所知，关于炎症小体遗传学对Mtb易感性和/或活动性结核发展的贡献仍然没有数据。因此，在来自巴西亚马逊地区一个流行区的活动性肺结核患者的病例/对照队列中分析了炎症小体基因中的选定多态性。我们的数据证明了NLRP3炎症小体编码基因多态性与活动性肺结核之间的新关联，并复制了在其他人群中观察到的P2X7与结核病之间的关联。这些结果强调了NLRP3炎症小体在人类结核病中的作用，并有助于我们了解参与活动性结核发展的途径，尽管需要更深入的研究来充分阐明该复合体在Mtb感染中的作用。
