Implications of SNPs on toll-like receptor genes in malaria: what do we know?

Costa, Allyson Guimarães; Ramasawmy, Rajendranath; Malheiro, Adriana; Lacerda, Marcus Vinícius Guimarães

doi:10.1590/0037-8682-0132-2017

Cited by 3 publications

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References 11 publications

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“…P . vivax presents biological complexity due to the interplay between environmental factors, parasite load, and the immunological status and genetic background of the human host [ 17 , 47 ]. The hypnozoite stage in the liver can cause clinical episodes of relapse with lower parasite load.…”

Section: Discussionmentioning

confidence: 99%

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Association of TLR variants with susceptibility to Plasmodium vivax malaria and parasitemia in the Amazon region of Brazil

et al. 2017

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BackgroundPlasmodium vivax malaria (Pv-malaria) is still considered a neglected disease despite an alarming number of individuals being infected annually. Malaria pathogenesis occurs with the onset of the vector-parasite-host interaction through the binding of pathogen-associated molecular patterns (PAMPs) and receptors of innate immunity, such as toll-like receptors (TLRs). The triggering of the signaling cascade produces an elevated inflammatory response. Genetic polymorphisms in TLRs are involved in susceptibility or resistance to infection, and the identification of genes involved with Pv-malaria response is important to elucidate the pathogenesis of the disease and may contribute to the formulation of control and elimination tools.Methodology/Principal findingsA retrospective case-control study was conducted in an intense transmission area of Pv-malaria in the state of Amazonas, Brazil. Genetic polymorphisms (SNPs) in different TLRs, TIRAP, and CD14 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 325 patients infected with P. vivax and 274 healthy individuals without malaria history in the prior 12 months from the same endemic area. Parasite load was determined by qPCR. Simple and multiple logistic/linear regressions were performed to investigate association between the polymorphisms and the occurrence of Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon) and T/T (TLR9 -1486C/T) genotypes appear to be risk factors for infection by P. vivax (TLR5: C/C vs. C/T [OR: 2.116, 95% CI: 1.054–4.452, p = 0.031]; TLR9: C/C vs. T/T [OR: 1.919, 95% CI: 1.159–3.177, p = 0.010]; respectively). Fever (COEF = 7599.46, 95% CI = 3063.80–12135.12, p = 0.001) and the C/C genotype of TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83–30540.44, p = 0.014) were independently associated with increased parasitemia in patients with Pv-malaria.ConclusionsVariants of TLRs may predispose individuals to infection by P. vivax. The TLR5 R392StopCodon and TLR9 -1486C/T variants are associated with susceptibility to Pv-malaria. Furthermore, the TLR9 variant -1237C/C correlates with high parasitemia.

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Section: Discussionmentioning

confidence: 99%

“…The inflammatory response resulting from the pathogenesis of the disease is closely related to the parasite load and the genetic background of the host [ 17 ]. Inflammation and cytokine production were reported to be higher in P .…”

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confidence: 99%

Association of TLR variants with susceptibility to Plasmodium vivax malaria and parasitemia in the Amazon region of Brazil

et al. 2017

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“…A evolução para quadros clínicos mais ou menos graves da doença em humanos está associada ao controle da parasitemia com maior ou menor efetividade, por meio da produção das citocinas inflamatórias TNF-α, IL 1, IL 6, IL 12 e IFN-γ (JIDE et al, 2009;UNDERHILL et al, 2003). Muitos estudos estão sendo realizados a fim de ampliar os conhecimentos da interação patógeno/humano, para elucidar papel do sistema imunológico, sobretudo das células dendríticas (YAP et al, 2019) e dos receptores do tipo Toll-like (TLRs) (COSTA et al, 2017) na fisiopatogenia e imunidade ao agente (STEVENSON et al, 2005). A compreensão da modulação do sistema imune hospedeiro pelo patógeno da malária, principalmente das células dendríticas, as mais importantes iniciadoras da resposta imune adaptativa, é essencial para o planejamento de vacinas eficazes (YAP et al, 2019).…”

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Malária: atualidades sobre a clínica, o diagnóstico e o tratamento

Will¹,

Andreon²,

Pereira³

et al. 2019

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A malária é um dos problemas de saúde pública mais graves do mundo, especialmente nos países em desenvolvimento, onde a taxa de mortalidade é mais alta. Os grupos mais vulneráveis são crianças, mulheres grávidas, pessoas com asplenia e viajantes provenientes de regiões endêmicas. Existem mais de 120 espécies de Plasmodium capazes de infectar aves, répteis e mamíferos, mas apenas seis estão relacionadas a infecções em humanos. O Plasmodium falciparum está envolvido nas formas mais graves da doença e está associado à malária cerebral e à morte. De fato, vários fatores contribuem para a gravidade da doença, que inclui o polimorfismo genético, o tamanho do inóculo plasmodial, a dinâmica populacional, a sensibilidade dos isolados a agentes químicos, a intensidade da imunidade antimalárica, coinfecções, o estado nutricional e idade do anfitrião, bem como o acesso aos serviços públicos de saúde. Todos esses fatores são um grande desafio ao tratamento de infecções, principalmente aquelas causadas por Plasmodium falciparum. Portanto, neste artigo discutimos alguns aspectos sobre o gênero Plasmodium, relacionados a manifestações clínicas, diagnóstico e aspectos terapêuticos da malária. Esta informação é relevante para os profissionais de saúde em geral.

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Polymorphisms in TLRs influence circulating cytokines production in Plasmodium vivax malaria

et al. 2018

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The efficiency of the immune system has been shaped throughout the evolutionary process allowing adaptations. In a Plasmodium vivax infection, the host attempts to develop an innate immune response to keep in check the parasite that is associated with inflammatory and regulatory processes. Production of pro-inflammatory and regulatory cytokines simultaneously appears to be a balancing mechanism for the host to prevent the onset of severe disease. Changes in the dynamics of circulating cytokines production can influence the pathogenesis, severity of the disease and episodes of recurrent Plasmodium vivax malaria (Pv-malaria). A cross-sectional study was conducted in endemic areas for Pv-malaria in the Amazonas State, Brazil. Several SNPs in TLR genes were genotyped by PCR-RFLP in 137 patients infected with P. vivax. Circulating cytokines IL-6, TNF, IL-2, IL-10, IFN-γ and IL-4 were measured by CBA. Influence of the studied SNPs on circulating cytokines was investigated by applying the Kruskal-Wallis test followed by Dunns' multiple comparison post-test. A Spearman correlation test also was performed to elaborate circulating cytokine networks and to demonstrate the level of interaction between each molecule. Individuals with genotypes A/G (TLR4 A299G), C/C (TLR6 S249P) and T/T (TLR9 -1486C/T) appear to produce less/gain IL-6, IFN-γ, IL-10, IL-2 and IL-4 compared to patients with wild-type and heterozygous genotypes. In addition, these genotypes seem to influence the interaction network between the molecules studied, causing a lower interaction, absence or even negative interaction between the cytokines. Data presented in this study suggests the influence of polymorphisms TLR4 (A299G), TLR6 (S249P) and TLR9 (-1486C/T) on the production of circulating cytokines during Pv-malaria.

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Implications of SNPs on toll-like receptor genes in malaria: what do we know?

Cited by 3 publications

References 11 publications

Association of TLR variants with susceptibility to Plasmodium vivax malaria and parasitemia in the Amazon region of Brazil

Association of TLR variants with susceptibility to Plasmodium vivax malaria and parasitemia in the Amazon region of Brazil

Malária: atualidades sobre a clínica, o diagnóstico e o tratamento

Polymorphisms in TLRs influence circulating cytokines production in Plasmodium vivax malaria

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