title: Contribution of inflammasome genetics in Plasmodium vivax malaria.
abstract: 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.
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Marina L S
authors.initials: MLS
authors.lastname: Santos
authors.affiliation: Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Edione Cristina
authors.initials: EC
authors.lastname: Reis
authors.affiliation: Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Bricher
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Tais N
authors.initials: TN
authors.lastname: Sousa
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Cristiana F A
authors.initials: CFA
authors.lastname: Brito
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Instituto de Pesquisas Leônidas and Maria Deane, Fundação Oswaldo Cruz, Manaus, AM, Brazil.
authors.forename: Marcus V G
authors.initials: MVG
authors.lastname: Lacerda
authors.affiliation: Hospital Julio Muller, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil.
authors.forename: Cor J F
authors.initials: CJF
authors.lastname: Fontes
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Luzia H
authors.initials: LH
authors.lastname: Carvalho
authors.affiliation: Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: alepontillo@usp.br.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pontillo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D058847:Inflammasomes / Q000235:genetics* / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015810:Linkage Disequilibrium; D016780:Malaria, Vivax / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D000070576:NLR Proteins; D010641:Phenotype; D010966:Plasmodium vivax; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000070576:NLR Proteins; C427903:NLRP1 protein, human
keywords: IL18; IL1B; Inflammasome; Malaria; NLRP1; NLRP3; P. vivax