Association of TLR2 and TLR6 gene polymorphism with Trichomoniasis vaginalis Infection
Abstract
Background: Toll-like receptors (TLR2 and TLR6) are a group of receptors that play a crucial role in the innate immune response and recognition of T. vaginalis. Single nucleotide polymorphisms (SNPs) in TLRs were manifested as important determinant affecting the susceptibility to trichomoniasis. This study aims to examine the impact of rs5743708 SNP in TLR2and rs5743810 SNP in TLR6 on Iraqi women infected with T. vaginalis.
Methods: Vaginal swabs and blood samples were isolated from 186 female patients who were admitting the gynecology clinics in three public hospitals in Babel governorate in Iraq. The collected samples were obtained for molecular identification of the parasite, sequencing of the TLR2 and TLR6 genes as well as performing the corresponding immunological studies.
Results: The PCR assays showed 40 positive women (95% CI, 15.85 to 28.11) of T. vaginalis β-tubulin gene. Genetic studies of rs5743708 SNP in TLR2 showed that the frequency of non-mutant G allele was clearly higher in infected women (37/64) than controls (27/64), and the GG genotype has significantly higher prevalence (90%) within infected women versus the GA (5%) and AA (5%) genotypes (p<0.001).Genetic analysis of rs5743810 SNP in TLR6, revealed that the mutant G allele was significantly higher in infected women (17/24) than healthy controls (5/24) (p=0.021), in addition, the heterozygous AG and the homozygous GG demonstrated significantly higher frequencies (13/16 and 2/3) in trichomoniasis women versus controls (3/13 and 1/3), respectively, p=0.013. Moreover, elevated concentrations of these two receptors were detected during T. vaginalis infection.
Conclusion: G allele of rs5743708 might play a protective role against trichomonas is for TLR2, and women homozygous for AA were not significantly associated with increased risk of trichomonas infection. While the mutant G allele of rs5743810 SNP may make women more sensitive for infection with T. vaginalis and subjects carrying AG heterozygous and GG homozygous genotypes might have higher risk of trichomoniasis compared with AA homozygous genotype. However, more studies are needed to confirm these findings and to understand the underlying involved mechanisms.
Full Text:
PDFReferences
Maritz JM, Land KM, Carlton JM, Hirt RP. What is the importance of zoonotic trichomonads for human health? Trends in Parasitology, (2014); 30(7): 333-341.
Coceres VM, Iriarte LS, Miranda-Magalhães A, Santos de Andrade TA, de Miguel N, Pereira-Neves A. Ultrastructural and Functional Analysis of a Novel Extra-Axonemal Structure in Parasitic Trichomonads. Frontiers in Cellular and Infection Microbiology, (2021); 9(11):757185.
Soper D. Trichomoniasis: under control or undercontrolled? American Journal of Obstetrics & Gynecology, (2004);190:281-290.
Lloyd GL, Case JR, De Frias D, Brannigan RE. Trichomonas vaginalis orchitis with associated severe oligoasthenoteratospermia and hypogonadism. Journal of Urology, (2003); 170: 924.
Sutcliffe S, Giovannucci E, Alderete JF, Chang TH, Gaydos CA, Zenilman JM, de Marzo AM, Willett WC, Platz EA. Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology, Biomarkers & Prevention, (2006); 15: 939-945.
Baxt LA, Baker RP, Singh U, Urban S. An Entamoeba histolytica rhomboid protease with atypical specificity cleaves a surface lectin involved in phagocytosis and immune evasion. Genes & Development, (2008); 22: 1636-1646.
Jiménez-Dalmaroni MJ, Gerswhin ME, Adamopoulos IE. The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review. Autoimmunity Reviews, (2016); 15(1): 1-8.
O'Neill LA. The role of MyD88-like adapters in Toll-like receptor signal transduction. Biochemical Society Transactions, (2003); 31(Pt3): 643-7.
Zariffard MR, Harwani S, Novak RM, Graham PJ, Ji X, Spear GT. Trichomonas vaginalis infection activates cells through toll-like receptor 4. Clinical Immunology, (2004); 111: 103- 107.
Chang JH, Park JY, Kim SK. Dependence on p38 MAPK signalling in the up-regulation of TLR2, TLR4 and TLR9 gene expression in Trichomonas vaginalis-treated HeLa cells. Immunology, (2006);118: 164-170.
Medvedev AE. Toll-like receptor polymorphisms, inflammatory and infectious diseases, allergies, and cancer. Journal of Interferon & Cytokine Research, (2013); 33(9): 467-84.
Valadkhani Z, Kazemi F, Hassan N, Aghighi Z, Esmaili I, Talebi M. Gene Diversity of Trichomonas vaginalis Isolates. Iranian Journal of Parasitology, (2011); 6(3): 101-6.
Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JA. Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Research, (2007); 35(Web Server issue): W71-4.
Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research, (1994); 22(22): 4673-80.
Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics, (2006); 22(15): 1928-9.
Mirzadeh M, Olfatifar M, Eslahi AV, Abdoli A, Houshmand E, Majidiani H, Johkool MG, Askari S, Hashemipour S, Badri M. Global prevalence of Trichomonas vaginalis among female sex workers: a systematic review and meta-analysis. Parasitology Research, (2021); 120(7): 2311-2322.
Simpson P, Higgins G, Qiao M, Waddell R, Kok T. Real-time PCRs for detection of Trichomonas vaginalis beta-tubulin and 18S rRNA genes in female genital specimens. Journal of Medical Microbiology, (2007); 56(Pt 6): 772-777.
Beyhan YE. A systematic review of Trichomonas vaginalis in Turkey from 2002 to 2020. Acta Tropica, (2021); 221: 105995.
Yadav s, Verma V, Yamini P, et al. Differential expression of Toll-like receptors in response to symptomatic and asymptomatic Trichomonas vaginalis infections. Research Square, (2022); DOI: 10.21203/rs.3.rs-2099711/v1.
Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA. A novel polymorphism in the Toll-like receptor 2 gene and its potential association with staphylococcal infection. Infection and Immunity, (2000); 68: 6398-6401.
Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, Coskun M, Cilli A, Yegin O. The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. European Respiratory Journal, (2004); 23(2): 219-23.
Bustamante J, Tamayo E, Flórez S, Telleria JJ, Bustamante E, López J, San Román JA, Alvarez FJ. El polimorfismo R753Q del toll-like receptor 2 se asocia a un aumento en el riesgo de sufrir endocarditis infecciosa [Toll-like receptor 2 R753Q polymorphisms are associated with an increased risk of infective endocarditis]. Revista Española de Cardiología, (2011); 64(11): 1056-9.
Randhawa AK, Shey MS, Keyser A, Peixoto B, Wells RD, de Kock M, Lerumo L, Hughes J, Hussey G, Hawkridge A, Kaplan G, Hanekom WA, Hawn TR; South African Tuberculosis Vaccine Initiative Team. Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants. PLoS Pathogens, (2011); 7(8): e1002174.
Leoratti FM, Farias L, Alves FP, Suarez-Mútis MC, Coura JR, Kalil J, Camargo EP, Moraes SL, Ramasawmy R. Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria. The Journal of Infectious Diseases, (2008); 198(5): 772-80.
Skevaki C, Pararas M, Kostelidou K, Tsakris A, Routsias JG. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious diseases. Clinical & Experimental Immunology, (2015); 180(2): 165-77.
Semlali A, Almutairi M, Rouabhia M, Reddy Parine N, Al Amri A, S Al-Numair N, M Hawsawi Y, Saud Alanazi M. Novel sequence variants in the TLR6 gene associated with advanced breast cancer risk in the Saudi Arabian population. PLoS One, (2018); 13(11): e0203376.
Li L, Li X, Gong P, Zhang X, Yang Z, Yang J, Li J. Trichomonas vaginalis Induces Production of Proinflammatory Cytokines in Mouse Macrophages Through Activation of MAPK and NF-κB Pathways Partially Mediated by TLR2. Frontiers in Microbiology, (2018); 9: 712.
Kim JA, Kim DK , Kang OH , Choi YA , Park HJ , Choi SC , Kim TH , Yun KJ , Nah YH , Lee YM. Inhibitory effect of luteolin on TNF-α-induced IL-8 production in human colon epithelial cells. International Immunopharmacology, (2005); 5: 209-217.
Ropert C, Gazzinelli RT. Regulatory role of Toll-like receptor 2 during infection with Trypanosoma cruzi. Journal of Endotoxin Research, (2004); 10: 425-430.
Schaefer TM, Desouza K, Fahey JV, Beagley KW, Wira CR. Toll-like receptor (TLR) expression and TLR-mediated cytokine/chemokine production by human uterine epithelial cells. Immunology, (2004); 112: 428-436.
Chandrani F, Alpana M, Snehasis D, Dipanjan C. TLR Signaling on Protozoan and Helminthic Parasite Infection [Online First], IntechOpen, (2019); DOI: 10.5772/intechopen.84711. Available from: https://www.intechopen.com/online-first/tlr-signaling-on-protozoan-and-helminthic-parasite-infection
DOI: http://dx.doi.org/10.62940/als.v10i0.2372
Refbacks
- There are currently no refbacks.