Santos Marina L S, Reis Edione Cristina, Bricher Pamela N, Sousa Tais N, Brito Cristiana F A, Lacerda Marcus V G, Fontes Cor J F, Carvalho Luzia H, Pontillo Alessandra
Laboratório de Malária, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
Infect Genet Evol. 2016 Jun;40:162-166. doi: 10.1016/j.meegid.2016.02.038. Epub 2016 Mar 3.
Recent reports showed that, in mice, symptomatic Plasmodium infection triggers NLRP3/NLRP12-dependent inflammasome formation and caspase-1 activation in monocytes. In humans, few works demonstrated that inflammasome is activated in malaria. As Plasmodiumvivax is a potent inducer of inflammatory response we hypothesised that inflammasome genetics might affect P. vivax malaria clinical presentation. For this purpose, selected SNPs in inflammasome genes were analysed among patients with symptomatic P. vivax malaria. 157 Brazilian Amazon patients with P. vivax malaria were genotyped for 10 single nucleotide polymorphisms (SNPs) in inflammasome genes NLRP1, NLRP3, AIM2, CARD8, IL1B, IL18 and MEFV. Effect of SNPs on hematologic and clinical parameters was analysed by multivariate analysis. Our data suggested an important role of NLRP1 inflammasome receptor in shaping the clinical presentation of P. vivax malaria, in term of presence of fever, anaemia and thrombocytopenia. Moreover IL1B rs1143634 resulted significantly associated to patients' parasitaemia, while IL18 rs5744256 plays a protective role against the development of anaemia. Polymorphisms in inflammasome genes could affect one or other aspects of malaria pathogenesis. Moreover, these data reveal novel aspects of P.vivax/host interaction that involved NLRP1-inflammasome.
最近的报告显示，在小鼠中，有症状的疟原虫感染会触发单核细胞中NLRP3/NLRP12依赖性炎性小体的形成和半胱天冬酶-1的激活。在人类中，很少有研究表明疟疾中炎性小体被激活。由于间日疟原虫是炎症反应的有效诱导剂，我们推测炎性小体基因可能会影响间日疟原虫疟疾的临床表现。为此，我们对有症状的间日疟原虫疟疾患者的炎性小体基因中的选定单核苷酸多态性（SNP）进行了分析。对157名巴西亚马逊地区的间日疟原虫疟疾患者进行了炎性小体基因NLRP1、NLRP3、AIM2、CARD8、IL1B、IL18和MEFV中10个单核苷酸多态性（SNP）的基因分型。通过多变量分析来分析SNP对血液学和临床参数的影响。我们的数据表明，就发热、贫血和血小板减少症的存在而言，NLRP1炎性小体受体在塑造间日疟原虫疟疾的临床表现方面起着重要作用。此外，IL1B rs1143634与患者的寄生虫血症显著相关，而IL18 rs5744256对贫血的发展起保护作用。炎性小体基因的多态性可能会影响疟疾发病机制的一个或其他方面。此外，这些数据揭示了间日疟原虫/宿主相互作用中涉及NLRP1炎性小体的新方面。
