Association of TLR7 and MyD88 Gene Polymorphism with Trichomoniasis vaginalis Infection
DOI:
https://doi.org/10.22317/jcms.v9i4.1390Keywords:
Trichomonas vaginalis, Trichomonas Infections, TLR7, MyD88, SNPsAbstract
Objective: Toll-like receptor 7 (TLR7) and MyD88 represent important components of the innate immune response which play a crucial role in recognition of T. vaginalis. Single nucleotide polymorphisms (SNPs) in TLRs and MyD88 were manifested as key determinant affecting the susceptibility to trichomoniasis. This study aims to examine the impact of two SNPs, designated rs179008 and rs4988453 in TLR7 and MyD88, respectively, on Iraqi women infected with T. vaginalis.
Methods: Women vaginal swabs as well as blood samples were collected from 186 female patients diagnosed clinically by gynecologists. These pateints were admitting the gynecology clinics in three public hospitals in Babel governorate in Iraq. Clinical samples were obtained for molecular identification of the parasite, sequencing of the TLR7 and MyD88 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 rs179008 SNP in TLR7 showed that the mutant T allele revealed significantly more prevalence in women infected with T. vaginalis in comparison with controls (p<0.001), furthermore, AT and TT genotypes distribution were significantly greater in patients than that in controls (p<0.01). Moreover, genetic analysis of rs4988453 SNP in MyD88 demonstrated that the mutant A allele almost has close frequency between patients and controls, and the heterozygous CA and homozygous AA genotypes were almost normally distributed between controls and patients. Finally, the concentrations of TLR7 and MyD88 were significantly elevated in the majority of women patients aged between 16-40 years.
Conclusion: The mutant allele A of rs4988453 SNP in MyD88 did not show an association with increased risk of trichomonas infection, however, the mutant allele T of rs179008 SNP in TLR7 might make women more sensitive for infection with T. vaginalis. However, more studies are needed to confirm these findings and to understand the underlying involved mechanisms.
References
Aggelou, K., Siapati, E. K., Gerogianni, I., Daniil, Z., Gourgoulianis, K., Ntanos, I., Simantirakis, E., Zintzaras, E., Mollaki, V., & Vassilopoulos, G. The -938C>A Polymorphism in MYD88 Is Associated with Susceptibility to Tuberculosis: A Pilot Study. Disease markers, 2016;4961086.
Akira, S., Uematsu, S., and Takeuchi, O. Pathogen recognition and innate immunity. Cell, 2006;124, 783–801.
Alseoudy MM, Elgamal M, Abdelghany DA, Borg AM, El-Mesery A, Elzeiny D, Hammad MO. Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study. Clin Immunol, 2022; 235, 108929.
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 Dev. 2008;22:1636–1646.
Beyhan YE. A systematic review of Trichomonas vaginalis in Turkey from 2002 to 2020. Acta Trop. 2021 Sep;221:105995. doi: 10.1016/j.actatropica.2021.105995. Epub 2021 Jun 5. PMID: 34097909.
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. Front Cell Infect Microbiol. 2021 Nov 9;11:757185. doi: 10.3389/fcimb.2021.757185. PMID: 34858875; PMCID: PMC8630684.
Daniil Z, Mollaki V, Malli F, Koutsokera A, Antoniou KM, Rodopoulou P, Gourgoulianis K, Zintzaras E, Vassilopoulos G. Polymorphisms and haplotypes in MyD88 are associated with the development of sarcoidosis: a candidate-gene association study. Mol Biol Rep, 2013;40(7), 4281-6.
Egan CE, Sukhumavasi W, Butcher BA, Denkers EY. Functional aspects of Toll-like receptor/MyD88 signalling during protozoan infection: focus on Toxoplasma gondii. Clin Exp Immunol,2009;156(1),17-24.
Fakhir FZ, Lkhider M, Badre W, Alaoui R, Meurs EF, Pineau P, Ezzikouri S, Benjelloun S. Genetic variations in toll-like receptors 7 and 8 modulate natural hepatitis C outcomes and liver disease progression. Liver Int, 2018;38(3),432-442.
Jiménez-Dalmaroni MJ, Gerswhin ME, Adamopoulos IE. The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review. Autoimmun Rev. 2016 Jan;15(1):1-8. doi: 10.1016/j.autrev.2015.08.009. Epub 2015 Aug 20. PMID: 26299984; PMCID: PMC4679489.
Klimosch, S. N., Försti, A., Eckert, J., Knezevic, J., Bevier, M., von Schönfels, W., Heits, N., Walter, J., Hinz, S., Lascorz, J., Hampe, J., Hartl, D., Frick, J. S., Hemminki, K., Schafmayer, C., & Weber, A. N. Functional TLR5 genetic variants affect human colorectal cancer survival. Cancer research, 2013;73(24), 7232–7242.
LaRosa DF, Stumhofer JS, Gelman AE, Rahman AH, Taylor DK, Hunter CA, Turka LA. T cell expression of MyD88 is required for resistance to Toxoplasma gondii. Proc Natl Acad Sci USA,2008;105(10),3855-60.
Lawing LF, Hedges SR, Schwebke JR. Detection of trichomonosis in vaginal and urine specimens from women by culture and PCR. J Clin Microbiol. 2000 Oct;38(10):3585-8. doi: 10.1128/JCM.38.10.3585-3588.2000. PMID: 11015368; PMCID: PMC87441.
Lin Yu-Ting. Toll-Like receptor polymorphism associations with Trichomonas vaginalis infection among African couples: A Hypothesis-generating Study. University of Washington, Seattle, Washington,2019.
Lloyd GL, Case JR, De Frias D, Brannigan RE. Trichomonas vaginalis orchitis with associated severe oligoasthenoteratospermia and hypogonadism. J Urol. 2003;170:924.
Mackelprang RD, Scoville CW, Cohen CR, Ondondo RO, Bigham AW, Celum C, et al. Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women. Genes Immunity, 2015;16, 362.
Mancuso, G., Gambuzza, M., Midiri, A., Biondo, C., Papasergi, S., Akira, S., Teti, G., and Beninati, C. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells. Nat. Immunol,2009;10,587–594.
Maritz JM, Land KM, Carlton JM, Hirt RP (2014). What is the importance of zoonotic trichomonads for human health? Trends Parasitol 30(7): 333-341.
Masha SC, Cools P, Sanders EJ, Vaneechoutte M, Crucitti T (2019). Trichomonas vaginalis and HIV infection acquisition: a systematic review and meta-analysis. Sex Transm Infect. 95(1):36-42.
Medvedev AE. Toll-like receptor polymorphisms, inflammatory and infectious diseases, allergies, and cancer. J Interferon Cytokine Res. 2013 Sep;33(9):467-84. doi: 10.1089/jir.2012.0140. Epub 2013 May 15. PMID: 23675778; PMCID: PMC3760066.
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. Parasitol Res. 2021 Jul;120(7):2311-2322. doi: 10.1007/s00436-021-07216-6. Epub 2021 Jun 25. PMID: 34170387.
Miya TV, Groome MJ, de Assis Rosa D. (2021). TLR genetic variation is associated with Rotavirus-specific IgA seroconversion in South African Black infants after two doses of Rotarix vaccine. Vaccine, 39(48), 7028-7035.
Nemati M, Larussa T, Khorramdelazad H, Mahmoodi M, Jafarzadeh A. Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection. Life Sci, 2017;178,17‐29.
Nishiya, Tadashi, Kajita, Emi, Horinouchi, Takahiro, Nishimoto, Arata and Miwa, Soichi. Distinct roles of TIR and non-TIR regions in the subcellular localization and signaling properties of MyD88, FEBS Letters, 2007;581.
Nouri Y, Weinkove R, Perret RT. Cell intrinsic Toll-like receptor signaling: implications for cancer immunotherapy and CAR T-cellsJournal for ImmunoTherapy of Cancer,2021;9,e003065.
Oh, D. Y., Baumann, K., Hamouda, O., Eckert, J. K., Neumann, K., Kücherer, C., Bartmeyer, B., Poggensee, G., Oh, N., Pruss, A., Jessen, H., & Schumann, R. R. (2009). A frequent functional toll-like receptor 7 polymorphism is associated with accelerated HIV-1 disease progression. AIDS (London, England), 23(3), 297–307.
O'Neill LA. The role of MyD88-like adapters in Toll-like receptor signal transduction. Biochem Soc Trans. 2003 Jun;31(Pt 3):643-7. doi: 10.1042/bst0310643. PMID: 12773173.
Patinote, C., Karroum, N. B., Moarbess, G., Cirnat, N., Kassab, I., Bonnet, P. A., & Deleuze-Masquéfa, C. Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes. European journal of medicinal chemistry, 2020;193,112238.
Rosentul, D. C., Delsing, C. E., Jaeger, M., Plantinga, T. S., Oosting, M., Costantini, I., Venselaar, H., Joosten, L. A., van der Meer, J. W., Dupont, B., Kullberg, B. J., Sobel, J. D., & Netea, M. G. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Frontiers in microbiology, 2014;5,483.
Royse KE, Kempf MC, McGwin G Jr, Wilson CM, Tang J, Shrestha S. (2012). Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents. J Reproduc Immunol, 96, 84–9.
Sánchez-Luquez K, Schadock IC, Gonçalves CV, Tornatore M, Finger-Jardim F, Avila EC, Soares MA, de Martínez AMB, Ellwanger JH, Chies JAB, da Hora VP. Impact of TLR7 and TLR9 polymorphisms on susceptibility to placental infections and pregnancy complications. J Reprod Immunol, 2021;146,103342.
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. J Med Microbiol. 2007 Jun;56(Pt 6):772-777. doi: 10.1099/jmm.0.47163-0. PMID: 17510262.
Song D, Li HH, Li HH, Dai J. Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer (Review). Oncol Lett,2015;10, 600–606.
Soper D. Trichomoniasis: under control or undercontrolled? Am J Obstet Gynecol. 2004;190:281–290.
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 Epidemiol Biomarkers Prev. 2006;15:939–945.
Taylor BD, Darville T, Ferrell RE, Kammerer CM, Ness RB, Haggerty CL. Variants in toll-like receptor 1 and 4 genes are associated with Chlamydia trachomatis among women with pelvic inflammatory disease. J Infect Dis, 2012;205,603-609.
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 Res. 1994 Nov 11;22(22):4673-80. doi: 10.1093/nar/22.22.4673. PMID: 7984417; PMCID: PMC308517.
Tryka KA, Hao L, Sturcke A, Jin Y, Wang ZY, Ziyabari L, Lee M, Popova N, Sharopova N, Kimura M, Feolo M. NCBI's Database of Genotypes and Phenotypes: dbGaP. Nucleic Acids Res, 2014;(Database issue), D975-9.
Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JA. Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res. 2007 Jul;35(Web Server issue):W71-4. doi: 10.1093/nar/gkm306. Epub 2007 May 7. PMID: 17485472; PMCID: PMC1933133.
Valadkhani Z, Kazemi F, Hassan N, Aghighi Z, Esmaili I, Talebi M. Gene Diversity of Trichomonas vaginalis Isolates. Iran J Parasitol. 2011 Aug;6(3):101-6. PMID: 22347304; PMCID: PMC3279894.
Xavier Solé, Elisabet Guinó, Joan Valls, Raquel Iniesta, Víctor Moreno, SNPStats: a web tool for the analysis of association studies, Bioinformatics, Volume 22, Issue 15, 1 August 2006, Pages 1928–1929.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Journal of Contemporary Medical Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
