Skip to main content

Advertisement

Log in

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

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Babu S, Blauvelt CP, Kumaraswami V, Nutman TB (2005) Diminished expression and function of TLR in lymphatic filariasis: a novel mechanism of immune dysregulation. J Immunol 175:1170–1176

    CAS  PubMed  Google Scholar 

  • Babu S, Blauvelt CP, Kumaraswami V, Nutman TB (2006) Cutting edge: diminished T cell TLR expression and function modulates the immune response in human filarial infection. J Immunol 176:3885–3889

    CAS  PubMed  Google Scholar 

  • Babu S, Bhat SQ, Kumar NP, Anuradha R, Kumaran P, Gopi PG, Kolappan C, Kumaraswami V, Nutman TB (2009) Attenuation of Toll-like receptor expression and function in latent tuberculosis by coexistent filarial infection with restoration following antifilarial chemotherapy. PLoS Negl Trop Dis 3:e489

    Article  PubMed  Google Scholar 

  • Bandi C, Trees AJ, Brattig NW (2001) Wolbachia in filarial nematodes: evolutionary aspects and implications for the pathogenesis and treatment of filarial diseases. Vet Parasitol 98:215–238

    Article  CAS  PubMed  Google Scholar 

  • Bazzocchi C, Jamnongluk W, O’Neill SL, Anderson TJ, Genchi C, Bandi C (2000) wsp gene sequences from the Wolbachia of filarial nematodes. Curr Microbiol 41:96–100

    Article  CAS  PubMed  Google Scholar 

  • Behbehani K (1998) Candidate parasitic diseases. Bull World Health Organ 76(Suppl 2):64–67

    PubMed  Google Scholar 

  • Ben-Ali M, Barbouche MR, Bousnina S, Chabbou A, Dellagi K (2004) Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin Diagn Lab Immunol 11:625–626

    CAS  PubMed  Google Scholar 

  • Brabin L (1990) Sex differentials in susceptibility to lymphatic filariasis and implications for maternal child immunity. Epidemiol Infect 105:335–353

    Article  CAS  PubMed  Google Scholar 

  • Brattig NW, Buttner DW, Hoerauf A (2001) Neutrophil accumulation around Onchocerca worms and chemotaxis of neutrophils are dependent on Wolbachia endobacteria. Microbes Infect 3:439–446

    Article  CAS  PubMed  Google Scholar 

  • Brattig NW, Bazzocchi C, Kirschning CJ, Reiling N, Buttner DW, Ceciliani F, Geisinger F, Hochrein H, Ernst M, Wagner H, Bandi C, Hoerauf A (2004) The major surface protein of Wolbachia endosymbionts in filarial nematodes elicits immune responses through TLR2 and TLR4. J Immunol 173:437–445

    CAS  PubMed  Google Scholar 

  • Capon F, Allen MH, Ameen M, Burden AD, Tillman D, Barker JN, Trembath RC (2004) A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum Mol Genet 13:2361–2368

    Article  CAS  PubMed  Google Scholar 

  • Carter KW, McCaskie PA, Palmer LJ (2006) JLIN: a Java based linkage disequilibrium plotter. BMC Bioinform 7:60

    Article  Google Scholar 

  • Chan SH, Dissanayake S, Mak JW, Ismail MM, Wee GB, Srinivasan N, Soo BH, Zaman V (1984) HLA and filariasis in Sri Lankans and Indians. Southeast Asian J Trop Med Public Health 15:281–286

    CAS  PubMed  Google Scholar 

  • Chanock SJ, Foster CB (1999) SNPing away at innate immunity. J Clin Invest 104:369–370

    Article  CAS  PubMed  Google Scholar 

  • Chen GL, Vallender EJ, Miller GM (2008) Functional characterization of the human TPH2 5′ regulatory region: untranslated region and polymorphisms modulate gene expression in vitro. Hum Genet 122:645–657

    Article  CAS  PubMed  Google Scholar 

  • Choi EH, Zimmerman PA, Foster CB, Zhu S, Kumaraswami V, Nutman TB, Chanock SJ (2001) Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India. Genes Immun 2:248–253

    Article  CAS  PubMed  Google Scholar 

  • Das PK, Manoharan A, Srividya A, Grenfell BT, Bundy DA, Vanamail P (1990) Frequency distribution of Wuchereria bancrofti microfilariae in human populations and its relationships with age and sex. Parasitology 101(Pt 3):429–434

    Article  PubMed  Google Scholar 

  • Debrah AY, Mand S, Toliat MR, Marfo-Debrekyei Y, Batsa L, Nurnberg P, Lawson B, Adjei O, Hoerauf A, Pfarr K (2007) Plasma vascular endothelial growth factor-A (VEGF-A) and VEGF-A gene polymorphism are associated with hydrocele development in lymphatic filariasis. Am J Trop Med Hyg 77:601–608

    CAS  PubMed  Google Scholar 

  • Derrigo M, Cestelli A, Savettieri G, Di Liegro I (2000) RNA–protein interactions in the control of stability and localization of messenger RNA (review). Int J Mol Med 5:111–123

    CAS  PubMed  Google Scholar 

  • Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV (2003) Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet 12:205–216

    Article  CAS  PubMed  Google Scholar 

  • Guilbert JJ (2003) The World Health Report 2002—reducing risks, promoting healthy life. Educ Health (Abingdon) 16:230

    Article  CAS  Google Scholar 

  • Haddix AC, Kestler A (2000) Lymphatic filariasis: economic aspects of the disease and programmes for its elimination. Trans R Soc Trop Med Hyg 94:592–593

    Article  CAS  PubMed  Google Scholar 

  • Haehnel V, Schwarzfischer L, Fenton MJ, Rehli M (2002) Transcriptional regulation of the human Toll-like receptor 2 gene in monocytes and macrophages. J Immunol 168:5629–5637

    CAS  PubMed  Google Scholar 

  • Hise AG, Daehnel K, Gillette-Ferguson I, Cho E, McGarry HF, Taylor MJ, Golenbock DT, Fitzgerald KA, Kazura JW, Pearlman E (2007) Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAM. J Immunol 178:1068–1076

    CAS  PubMed  Google Scholar 

  • Hoerauf A, Volkmann L, Hamelmann C, Adjei O, Autenrieth IB, Fleischer B, Buttner DW (2000) Endosymbiotic bacteria in worms as targets for a novel chemotherapy in filariasis. Lancet 355:1242–1243

    Article  CAS  PubMed  Google Scholar 

  • Johnson CM, Tapping RI (2007) Microbial products stimulate human Toll-like receptor 2 expression through histone modification surrounding a proximal NF-kappaB-binding site. J Biol Chem 282:31197–31205

    Article  CAS  PubMed  Google Scholar 

  • Lamb TJ, Le Goff L, Kurniawan A, Guiliano DB, Fenn K, Blaxter ML, Read AF, Allen JE (2004) Most of the response elicited against Wolbachia surface protein in filarial nematode infection is due to the infective larval stage. J Infect Dis 189:120–127

    Article  CAS  PubMed  Google Scholar 

  • Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145

    Article  CAS  PubMed  Google Scholar 

  • Meyrowitsch DW, Simonsen PE, Garred P, Dalgaard M, Magesa SM, Alifrangis M (2010) Association between mannose-binding lectin polymorphisms and Wuchereria bancrofti infection in two communities in north-eastern Tanzania. Am J Trop Med Hyg 82:115–120

    Article  CAS  PubMed  Google Scholar 

  • Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  CAS  PubMed  Google Scholar 

  • Noguchi E, Nishimura F, Fukai H, Kim J, Ichikawa K, Shibasaki M, Arinami T (2004) An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population. Clin Exp Allergy 34:177–183

    Article  CAS  PubMed  Google Scholar 

  • Nuchprayoon S, Junpee A, Poovorawan Y, Scott AL (2005) Detection and differentiation of filarial parasites by universal primers and polymerase chain reaction–restriction fragment length polymorphism analysis. Am J Trop Med Hyg 73:895–900

    CAS  PubMed  Google Scholar 

  • Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, Coskun M, Cilli A, Yegin O (2004) The Arg753GLn polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur Respir J 23:219–223

    Article  CAS  PubMed  Google Scholar 

  • Punkosdy GA, Addiss DG, Lammie PJ (2003) Characterization of antibody responses to Wolbachia surface protein in humans with lymphatic filariasis. Infect Immun 71:5104–5114

    Article  CAS  PubMed  Google Scholar 

  • Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575

    Article  CAS  PubMed  Google Scholar 

  • Sauna ZE, Kimchi-Sarfaty C, Ambudkar SV, Gottesman MM (2007) Silent polymorphisms speak: how they affect pharmacogenomics and the treatment of cancer. Cancer Res 67:9609–9612

    Article  CAS  PubMed  Google Scholar 

  • Schroder NW, Schumann RR (2005) Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis 5:156–164

    PubMed  Google Scholar 

  • Subrahmanyam D, Mehta K, Nelson DS, Rao YV, Rao CK (1978) Immune reactions in human filariasis. J Clin Microbiol 8:228–232

    CAS  PubMed  Google Scholar 

  • Tahara T, Arisawa T, Wang F, Shibata T, Nakamura M, Sakata M, Hirata I, Nakano H (2007) Toll-like receptor 2-196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer. Cancer Sci 98:1790–1794

    Article  CAS  PubMed  Google Scholar 

  • Takeda K, Takeuchi O, Akira S (2002) Recognition of lipopeptides by Toll-like receptors. J Endotoxin Res 8:459–463

    CAS  PubMed  Google Scholar 

  • World Health Organization (1995) The World Health Report 1995—bridging the gaps. World Health Forum 16:377–385

    Google Scholar 

  • Thuong NT, Hawn TR, Thwaites GE, Chau TT, Lan NT, Quy HT, Hieu NT, Aderem A, Hien TT, Farrar JJ, Dunstan SJ (2007) A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes Immun 8:422–428

    Article  CAS  PubMed  Google Scholar 

  • Tisch DJ, Hazlett FE, Kastens W, Alpers MP, Bockarie MJ, Kazura JW (2001) Ecologic and biologic determinants of filarial antigenemia in bancroftian filariasis in Papua New Guinea. J Infect Dis 184:898–904

    Article  CAS  PubMed  Google Scholar 

  • Triteeraprapab S, Kanjanopas K, Suwannadabba S, Sangprakarn S, Poovorawan Y, Scott AL (2000) Transmission of the nocturnal periodic strain of Wuchereria bancrofti by Culex quinquefasciatus: establishing the potential for urban filariasis in Thailand. Epidemiol Infect 125:207–212

    Article  CAS  PubMed  Google Scholar 

  • Triteeraprapab S, Nuchprayoon I, Porksakorn C, Poovorawan Y, Scott AL (2001) High prevalence of Wuchereria bancrofti infection among Myanmar migrants in Thailand. Ann Trop Med Parasitol 95:535–538

    Article  CAS  PubMed  Google Scholar 

  • Turner JD, Langley RS, Johnston KL, Gentil K, Ford L, Wu B, Graham M, Sharpley F, Slatko B, Pearlman E, Taylor MJ (2009) Wolbachia lipoprotein stimulates innate and adaptive immunity through Toll-like receptors 2 and 6 to induce disease manifestations of filariasis. J Biol Chem 284:22364–22378

    Article  CAS  PubMed  Google Scholar 

  • van der Stoep N, Quinten E, van den Elsen PJ (2002) Transcriptional regulation of the MHC class II trans-activator (CIITA) promoter III: identification of a novel regulatory region in the 5′-untranslated region and an important role for cAMP-responsive element binding protein 1 and activating transcription factor-1 in CIITA-promoter III transcriptional activation in B lymphocytes. J Immunol 169:5061–5071

    PubMed  Google Scholar 

  • Velez DR, Wejse C, Stryjewski ME, Abbate E, Hulme WF, Myers JL, Estevan R, Patillo SG, Olesen R, Tacconelli A, Sirugo G, Gilbert JR, Hamilton CD, Scott WK (2010) Variants in Toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. Hum Genet 127:65–73

    Article  CAS  PubMed  Google Scholar 

  • Venugopal PG, Nutman TB, Semnani RT (2009) Activation and regulation of Toll-like receptors (TLRs) by helminth parasites. Immunol Res 43:252–263

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Tahara T, Arisawa T, Shibata T, Nakamura M, Fujita H, Iwata M, Kamiya Y, Nagasaka M, Takahama K, Watanabe M, Hirata I, Nakano H (2007) Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis. J Gastroenterol Hepatol 22:925–929

    Article  CAS  PubMed  Google Scholar 

  • Yazdanbakhsh M, Abadi K, de Roo M, van Wouwe L, Denham D, Medeiros F, Verduijn W, Schreuder GM, Schipper R, Giphart MJ, de Vries RR (1997) HLA and elephantiasis revisited. Eur J Immunogenet 24:439–442

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was financially supported by Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University and the National Research Council of Thailand. AJ and VS are supported by The Royal Golden Jubilee PhD Program, The Thailand Research Fund. We would like to thank Dr. Saravudh Suvannadabba, Dr. Anupong Chitvarakorn, and the entire staff of the Filariasis Division and regional officers for their assistance in specimen collection.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Surang Nuchprayoon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Junpee, A., Tencomnao, T., Sanprasert, V. et al. Association between Toll-like receptor 2 (TLR2) polymorphisms and asymptomatic bancroftian filariasis. Parasitol Res 107, 807–816 (2010). https://doi.org/10.1007/s00436-010-1932-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-010-1932-9

Keywords

Navigation