Possible role of TLR4 and TLR9 SNPs in protection against congenital toxoplasmosis

Abstract

The purpose of this investigation was the determination of the distribution of genotypes at single nucleotide polymorphisms (SNPs) of the toll-like receptor 4 (TLR4) and the toll-like receptor 9 (TLR9) in fetuses and newborns congenitally infected with Toxoplasma gondii and the identification of genetic changes predisposing to infection development. The study involved 20 fetuses and newborns with congenital toxoplasmosis and 50 uninfected controls. The levels of IgG and IgM antibodies against T. gondii, as well as IgG avidity, were estimated by enzyme-linked fluorescent assay (ELFA) tests. T. gondii DNA loads in amniotic fluids were assayed by the real-time (RT) quantitative polymerase chain reaction (Q PCR) technique for parasitic B1 gene. TLR4 and TLR9 SNPs were identified using a self-designed multiplex nested PCR-restriction fragment length polymorphism (RFLP) assay. Randomly selected genotypes at SNPs were confirmed by sequencing. All the genotypes were tested for Hardy–Weinberg equilibrium and TLR4 genotypes were analyzed for linkage disequilibrium. A correlation was studied between the genotypes or haplotypes and the development of congenital toxoplasmosis using a logistic regression model. Single SNP analysis showed no statistically significant differences in the distribution of distinct genotypes at the analyzed TLR4 and TLR9 SNPs between T. gondii-infected fetuses and newborns and the controls. Taking into account the prevalence of alleles residing within polymorphic sites, similar prevalence rates were observed in both of the studied groups. The multiple SNP analysis indicated GTG variants at the TLR4 and TLR9 SNPs to be significantly less frequent in offspring with congenital toxoplasmosis than in uninfected offspring (p ≤ 0.0001). TLR4 and TLR9 SNPs seem to be involved in protection against congenital toxoplasmosis.

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

“…The authors of a previous study reported that the TLR9 gene causes an intracellular receptor signal cascade, and thus evokes nuclear transcription factors resulting in the production of pro-and anti-inflammatory cytokines (Hemmi et al, 2000). The authors of previous studies have reported that TLR9 gene polymorphisms are associated with the development of several inflammatory diseases (Bharti et al, 2014;Berenson et al, 2015;Trejo-de la O et al, 2015;Wen et al, 2015;Wujcicka et al, 2015). Bharti et al (2014) conducted a study in a Chinese population and assessed the association between TLR9 polymorphisms and pulmonary tuberculosis; they found that the TLR9 rs187084 polymorphism was associated with reduced risk of pulmonary tuberculosis.…”

Toll-like receptors genes polymorphisms and the occurrence of HCMV infection among pregnant women

“…1), were genotyped, using the self-designed nested PCR-RFLP assays. The sequences of the external and internal primers, the lengths of PCR products and annealing temperatures, used in the PCR assays for TLR SNPs, were previously shown [18, 28, 44]. The sequences, annealing temperatures, and the sizes of amplicons for TLR SNPs are presented in Table 1.…”

Toxoplasmosis and Public Health Genomics

“…Andrade et al [38] have demonstrated TLR7 and TLR9 sense T. gondii-associated nucleic acids (DNA or RNA) while TLR11 and TLR12 sense Toxoplasma profiling. Thus, understanding genomic variations in TLR is important to highlight immune defense against T. gondii [30,39,40]. NOD-like receptor (NLR) families are important for immediate responses against structures that are present in T. gondii like TLR receptors.…”