Association between Toll-like receptor 2 (TLR2) polymorphisms and asymptomatic bancroftian filariasis

Abstract

Lymphatic filariasis is mainly caused by the filarial nematodes Wuchereria bancrofti and Brugia malayi. Wolbachia, intracellular symbiotic bacteria in filarial parasite, is known to induce immune response predominantly through Toll-like receptor 2 (TLR2). This study was performed to investigate the association between polymorphisms of the TLR2 gene and susceptibility to asymptomatic bancroftian filariasis. A total of 142 unrelated asymptomatic bancroftian filariasis patients and 151 endemic normal controls in Tak province, Thailand were recruited into this study. The -196 to -173 deletion (del) polymorphism in the 5' untranslated region was investigated by allele-specific polymerase chain reaction. Two single nucleotide polymorphisms, +597 T>C and +1350 T>C, in exon 3 were identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Furthermore, we analyzed the functional difference between the TLR2 -196 to -173 del and wild-type (wt) alleles using the luciferase reporter assay. All three polymorphisms were associated with a higher risk of asymptomatic bancroftian filariasis and were in strong linkage disequilibrium with each other. The TLR2 haplotype -196 to -173del/+597C/+1350C was strongly associated with an increased risk of asymptomatic bancroftian filariasis. The TLR2 -196 to -173 del allele had a significantly lower transcriptional activity than wt allele. The results of our study indicate that TLR2 -196 to -173 del, +597 T>C and +1350 T>C polymorphisms are associated with asymptomatic bancroftian filariasis in Thailand. Our functional study also supports this finding with respect to differential TLR2 gene expression by -196 to -173 del polymorphism.

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

“…Moreover, associations between the TLR2 genetic diversity and Alzheimer's disease [61] or cognitive function in schizophrenia [62] are highly suggestive of genetically-driven inter-individual ability to modulate neuroinflammatory processes. Of importance is that the TLR2 rs3804099 polymorphism was showed on the one hand to be associated with several inflammatory and infectious diseases including pulmonary tuberculosis, neonatal infection, filariasis, ocular Behcet's disease and cancer [63][64][65][66][67] and to exert a functional impact on the inflammatory response on the other [65,68,69].…”

Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

“…Once PAMPs are recognized by leucine-rich domains, the signal cascades are initiated, and remarkable proinflammatory cytokines and chemokines, as well as costimulatory molecules, are ultimately induced through the activation of a variety of transcriptional complexes including NF-κB and AP-1 [11][12][13][14][15]. Additionally, host susceptibility to infectious diseases may be associated with the TLRs' polymorphisms [16][17][18].…”

Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

“…However, some infections have been associated with TLR polymorphisms. The TLR2 haplotype 196-174 del was found to be strongly associated with an increased risk of asymptomatic bancroftian filariasis [9]. In a study on neurocysticircosis (NCC), TLR4 Asp299Gly and Thr399Ile polymorphisms were associated with its occurrence (P < 0.001 for Asp299Gly; P = 0.003 for Thr399Ile) and progression to symptomatic NCC, compared with control subjects or asymptomatic NCC [20].…”

“…Various TLR polymorphisms have been implicated in susceptibility and progression of diseases like neurocysticercosis, Hepatitis C virus, asthma, cervical cancer and asymptomatic filariasis [9]- [11]. A few previous studies have reported that intestinal and biliary invasion of Cryptosporidium spp.…”