Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-26T11:55:13.878Z Has data issue: false hasContentIssue false
  • English
  • Français

Reduced Trichomonas vaginalis viability in mice pretreated with parasite DNA

Published online by Cambridge University Press:  28 August 2019

Marco Antonio Barajas-Mendiola ,
Laura E. Castellano ,
Miriam Barrios-Rodiles ,
Martha A. Deveze-Alvarez ,
Eva E. Avila  and
Patricia Cuéllar-Mata Open the ORCID record for Patricia Cuéllar-Mata [Opens in a new window]
Marco Antonio Barajas-Mendiola
Affiliation:
Departamento de Biología, Universidad de Guanajuato, Guanajuato, Mexico
Laura E. Castellano
Affiliation:
Departamento de Ingenierías Química, Electrónica y Biomédica, Universidad de Guanajuato, Guanajuato, Mexico
Miriam Barrios-Rodiles
Affiliation:
Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
Martha A. Deveze-Alvarez
Affiliation:
Departamento de Farmacia, Universidad de Guanajuato, Guanajuato, Mexico
Eva E. Avila
Affiliation:
Departamento de Biología, Universidad de Guanajuato, Guanajuato, Mexico
Patricia Cuéllar-Mata*
Affiliation:
Departamento de Biología, Universidad de Guanajuato, Guanajuato, Mexico
*
Author for correspondence: Patricia Cuéllar-Mata, E-mail: mata@ugto.mx
Get access Rights & Permissions [Opens in a new window]

Abstract

Trichomonas vaginalis is an extracellular parasite that colonizes the human urogenital tract leading to trichomoniasis, the most common sexually-transmitted non-viral disease worldwide. The immune response plays a critical role in the host defense against this parasite. Trichomonas' DNA contains unmethylated CpG motifs (CpGDNA) that in other microorganisms act as modulators of the immune response. However, the molecular mechanisms responsible for CpGDNA immune modulation are still unclear. As macrophages participate in the first line of defense against infection, we investigated the type of immune response of murine macrophages to T. vaginalis DNA (TvDNA). We observed high expression of the proinflammatory cytokines IL-6 and IL-12p40 in macrophages stimulated with TvDNA. In contrast, the anti-inflammatory response, assessed by IL-10 and IL-13 mRNA expression was delayed. This suggests that the immune response induced by TvDNA is modulated through cytokine production, mediated partly by NADPH-oxidase activity, as TvDNA induced reactive species of oxygen production and a rounded morphology in macrophages indicative of an M1 phenotype. Furthermore, infected mice pretreated with TvDNA displayed persistent vulvar inflammation and decreased parasite viability consistent with higher proinflammatory cytokine levels during infection compared to untreated mice. Overall, our findings suggest that TvDNA pretreatment modulates the immune response favouring parasite elimination.

Keywords

Macrophage polarizationparasite DNAparasite viabilityTrichomonas vaginalis
Type
Research Article
Information
Parasitology , Volume 146 , Issue 13 , November 2019 , pp. 1636 - 1645
Check for updates
Copyright
Copyright © Cambridge University Press 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abou Fakher, FH, Rachinel, N, Klimczak, M, Louis, J and Doyen, N (2009) TLR9-dependent activation of dendritic cells by DNA from Leishmania major favors Th1 cell development and the resolution of lesions. Journal of Immunology 182, 1386–1396.Google Scholar
Ahmad-Nejad, P, Häcker, H, Rutz, M, Bauer, S, Vabulas, RM and Wagner, H (2002) Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. European Journal of Immunology 32, 1958–1968.Google Scholar
Arias-Negrete, S, Jiménez-Romero, LA, Solís-Martínez, MO, Ramírez-Emiliano, J, Avila, EE and Cuéllar-Mata, P (2004) Indirect determination of nitric oxide production by reduction of nitrate with a freeze-thawing-resistant nitrate reductase from Escherichia coli MC1061. Analytical Biochemistry 328, 14–21.Google Scholar
Bogdan, C (2015) Nitric oxide synthase in innate and adaptive immunity: an update. Trends in Immunology 36, 161–178.Google Scholar
Broz, P and Monack, DM (2013) Newly described pattern recognition receptors team up against intracellular pathogens. Nature Reviews Immunology 13, 551–565.Google Scholar
Choi, HS, Kim, JW, Cha, YN and Kim, C (2006) A quantitative nitroblue tetrazolium assay for determining intracellular superoxide anion production in phagocytic cells. Journal of Immunoassay & Immunochemistry 27, 31–44.Google Scholar
Chu, RS, Targoni, OS, Krieg, AM, Lehmann, PV and Harding, CV (1997) Cpg oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. Journal of Experimental Medicine 186, 1623–1631.Google Scholar
da Costa, RF, de Souza, W, Benchimol, M, Alderete, JF and Morgado-Diaz, JA (2005) Trichomonas vaginalis perturbs the junctional complex in epithelial cells. Cell Research 15, 704–716.Google Scholar
Das, S, Ghosh, AK, Singh, S, Saha, B, Ganguly, A and Das, P (2015) Unmethylated CpG motifs in the L. donovani DNA regulate TLR9-dependent delay of programmed cell death in macrophages. Journal of Leukocyte Biology 97, 363–378.Google Scholar
Dunne, RL, Dunn, LA, Upcroft, P, O'Donoghue, PJ and Upcroft, JA (2003) Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis. Cell Research 13, 239–249.Google Scholar
Ehrlich, AK, Fernández, OL, Rodriguez-Pinto, D, Castilho, TM, Corral Caridad, MJ, Goldsmith-Pestana, K, Saravia, NG and McMahon-Pratt, D (2017) Local delivery of the toll-like receptor 9 ligand CpG downregulates host immune and inflammatory responses, ameliorating established Leishmania (Viannia) panamensis chronic infection. Infection and Immunity 85, 1–6.Google Scholar
Farrokhi, S, Abbasirad, N, Movahed, A, Khazaei, HA, Pishjoo, M and Rezaei, N (2017) TLR9-based immunotherapy for the treatment of allergic diseases. Immunotherapy 9, 339–346.Google Scholar
Forman, HJ and Torres, M (2002) Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling. American Journal of Respiratory and Critical Care Medicine 166, S4–S8.Google Scholar
Fraternale, A, Brundu, S and Magnani, M (2015) Polarization and repolarization of macrophages. Journal of Clinical & Cellular Immunology 6, 2.Google Scholar
Galanos, C, Lüderitz, O, Rietschel, ET, Westphal, O, Brade, H, Brade, L, Freudenberg, M, Schade, U, Imoto, M and Yoshimura, H (1985) Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. European Journal of Biochemistry 148, 1–5.Google Scholar
Ghosh, I, Muwonge, R, Mittal, S, Banerjee, D, Kundu, P, Mandal, R, Biswas, J and Basu, P (2017) Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions. Journal of Clinical Virology 87, 43–48.Google Scholar
Gong, P, Cao, L, Guo, Y, Dong, H, Yuan, S, Yao, X, Ren, W, Yao, L, Xu, Z, Sun, Q and Zhang, X (2016) Toxoplasma gondii: protective immunity induced by a DNA vaccine expressing GRA1 and MIC3 against toxoplasmosis in BALB/c mice. Experimental Parasitology 166, 131–136.Google Scholar
Gordon, S (2003) Alternative activation of macrophages. Nature Reviews Immunology 3, 23–35.Google Scholar
Gupta, CL, Akhtar, S, Waye, A, Pandey, NR, Pathak, N and Bajpai, P (2015) Cross talk between Leishmania donovani CpG DNA and Toll-like receptor 9: an immunoinformatics approach. Biochemical and Biophysical Research Communications 459, 424–429.Google Scholar
Halperin, SA, Van Nest, G, Smith, B, Abtahi, S, Whiley, H and Eiden, JJ (2003) A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. Vaccine 21, 2461–2467.Google Scholar
Han, IH, Goo, SY, Park, SJ, Hwang, SJ, Kim, YS, Yang, MS, Ahn, MH and Ryu, JS (2009) Proinflammatory cytokine and nitric oxide production by human macrophages stimulated with Trichomonas vaginalis. Korean Journal of Parasitology 47, 205–212.Google Scholar
Hemmi, H, Takeuchi, O, Kawai, T, Kaisho, T, Sato, S, Sanjo, H, Matsumoto, M, Hoshino, K, Wagner, H, Takeda, K and Akira, S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740–745.Google Scholar
Holmgren, J and Czerkinsky, C (2005) Mucosal immunity and vaccines. Nature Medicine 11, S45–S53.Google Scholar
Iho, S, Maeyama, J and Suzuki, F (2015) Cpg oligodeoxynucleotides as mucosal adjuvants. Human Vaccines & Immunotherapeutics 11, 755–760.Google Scholar
Iwasaki, A and Medzhitov, R (2015) Control of adaptive immunity by the innate immune system. Nature Immunology 16, 343–353.Google Scholar
Jones, PA and Takai, D (2001) The role of DNA methylation in mammalian epigenetics. Science 293, 1068–1070.Google Scholar
Kowluru, A and Kowluru, RA (2014) Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of glucolipotoxicity and diabetes. Biochemical Pharmacology 88, 275–283.Google Scholar
Krieg, AM (2000) The role of CpG motifs in innate immunity. Current Opinion in Immunology 12, 35–43.Google Scholar
Krieg, AM (2002) Cpg motifs in bacterial DNA and their immune effects. Annual Review of Immunology 20, 709–760.Google Scholar
Kumar, H, Kawai, T and Akira, S (2011) Pathogen recognition by the innate immune system. International Reviews of Immunology 30, 16–34.Google Scholar
Latz, E, Schoenemeyer, A, Visintin, A, Fitzgerald, KA, Monks, BG, Knetter, CF, Lien, E, Nilsen, NJ, Espevik, T and Golenbock, DT (2004) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nature Immunology 5, 190–198.Google Scholar
Lazenby, GB, Unal, ER, Andrews, AL and Simpson, K (2014) Cost-effectiveness analysis of annual Trichomonas vaginalis screening and treatment in HIV-positive women to prevent HIV transmission. Sexually Transmitted Diseases 41, 353–358.Google Scholar
Martinez, FO and Gordon, S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000prime Reports 6, 13.Google Scholar
McGhee, JR, Mestecky, J, Dertzbaugh, MT, Eldridge, JH, Hirasawa, M and Kiyono, H (1992) The mucosal immune system: from fundamental concepts to vaccine development. Vaccine 10, 75–88.Google Scholar
McWhorter, FY, Davis, CT and Liu, WF (2015) Physical and mechanical regulation of macrophage phenotype and function. Cellular and Molecular Life Sciences 72, 1303–1316.Google Scholar
Messina, JP, Gilkeson, GS and Pisetsky, DS (1991) Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA. Journal of Immunology 147, 1759–1764.Google Scholar
Mielczarek, E and Blaszkowska, J (2016) Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure. Infection 44, 447–458.Google Scholar
Moseman, EA, Liang, X, Dawson, AJ, Panoskaltsis-Mortari, A, Krieg, AM, Liu, YJ, Blazar, BR and Chen, W (2004) Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. Journal of Immunology 173, 4433–4442.Google Scholar
Murray, PJ (2017) Macrophage polarization. Annual Review of Physiology 79, 541–566.Google Scholar
Murray, PJ, Allen, JE, Biswas, SK, Fisher, EA, Gilroy, DW, Goerdt, S, Gordon, S, Hamilton, JA, Ivashkiv, LB, Lawrence, T, Locati, M, Mantovani, A, Martinez, FO, Mege, JL, Mosser, DM, Natoli, G, Saeij, JP, Schultze, JL, Shirey, KA, Sica, A, Suttles, J, Udalova, I, van Ginderachter, JA, Vogel, SN and Wynn, TA (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41, 14–20.Google Scholar
Newman, L, Rowley, J, Vander Hoorn, S, Wijesooriya, NS, Unemo, M, Low, N, Stevens, G, Gottlieb, S, Kiarie, J and Temmerman, M (2015) Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One 10, e0143304.Google Scholar
Olmos-Ortiz, LM, Barajas-Mendiola, MA, Barrios-Rodiles, M, Castellano, LE, Arias-Negrete, S, Avila, EE and Cuéllar-Mata, P (2017) Trichomonas vaginalis exosome-like vesicles modify the cytokine profile and reduce inflammation in parasite-infected mice. Parasite Immunology 39(6).Google Scholar
Pasare, AJaC (2017) Innate control of adaptive immunity: beyond the three-signal paradigm. Journal of Immunology 198, 3791–3800.Google Scholar
Pautz, A, Art, J, Hahn, S, Nowag, S, Voss, C and Kleinert, H (2010) Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 23, 75–93.Google Scholar
Pereira-Neves, A and Benchimol, M (2007) Phagocytosis by Trichomonas vaginalis: new insights. Biology of the Cell 99, 87–101.Google Scholar
Raetz, CR and Whitfield, C (2002) Lipopolysaccharide endotoxins. Annual Review of Biochemistry 71, 635–700.Google Scholar
Ramirez, L, Corvo, L, Duarte, MC, Chávez-Fumagalli, MA, Valadares, DG, Santos, DM, de Oliveira, CI, Escutia, MR, Alonso, C, Bonay, P, Tavares, CA, Coelho, EA and Soto, M (2014) Cross-protective effect of a combined L5 plus L3 Leishmania major ribosomal protein based vaccine combined with a Th1 adjuvant in murine cutaneous and visceral leishmaniasis. Parasites & Vectors 7, 3.Google Scholar
Rodríguez-Morales, O, Monteón-Padilla, V, Carrillo-Sánchez, SC, Rios-Castro, M, Martínez-Cruz, M, Carabarin-Lima, A and Arce-Fonseca, M (2015) Experimental vaccines against Chagas disease: a journey through history. Journal of Immunology Research 2015, 489758.Google Scholar
Ryan, CM, de Miguel, N and Johnson, PJ (2011) Trichomonas vaginalis: current understanding of host–parasite interactions. Essays in biochemistry 51, 161–175.Google Scholar
Rynkiewicz, D, Rathkopf, M, Sim, I, Waytes, AT, Hopkins, RJ, Giri, L, DeMuria, D, Ransom, J, Quinn, J, Nabors, GS and Nielsen, CJ (2011) Marked enhancement of the immune response to BioThrax® (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers. Vaccine 29, 6313–6320.Google Scholar
Sabatel, C, Radermecker, C, Fievez, L, Paulissen, G, Chakarov, S, Fernandes, C, Olivier, S, Toussaint, M, Pirottin, D, Xiao, X, Quatresooz, P, Sirard, JC, Cataldo, D, Gillet, L, Bouabe, H, Desmet, CJ, Ginhoux, F, Marichal, T and Bureau, F (2017) Exposure to bacterial CpG DNA protects from airway allergic inflammation by expanding regulatory lung interstitial macrophages. Immunity 46, 457–473.Google Scholar
Schletter, J, Heine, H, Ulmer, AJ and Rietschel, ET (1995) Molecular mechanisms of endotoxin activity. Archives of Microbiology 164, 383–389.Google Scholar
Shivahare, R, Vishwakarma, P, Parmar, N, Yadav, PK, Haq, W, Srivastava, M, Gupta, S and Kar, S (2014) Combination of liposomal CpG oligodeoxynucleotide 2006 and miltefosine induces strong cell-mediated immunity during experimental visceral leishmaniasis. PLoS One 9, e94596.Google Scholar
Shoda, LK, Kegerreis, KA, Suarez, CE, Roditi, I, Corral, RS, Bertot, GM, Norimine, J and Brown, WC (2001) DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T. brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor alpha, and nitric oxide. Infection and Immunity 69, 2162–2171.Google Scholar
Shui, IM, Kolb, S, Hanson, C, Sutcliffe, S, Rider, JR and Stanford, JL (2016) Trichomonas vaginalis infection and risk of advanced prostate cancer. Prostate 76, 620–623.Google Scholar
Sica, A, Erreni, M, Allavena, P and Porta, C (2015) Macrophage polarization in pathology. Cellular and Molecular Life Sciences 72, 4111–4126.Google Scholar
Silver, BJ, Guy, RJ, Kaldor, JM, Jamil, MS and Rumbold, AR (2014) Trichomonas vaginalis as a cause of perinatal morbidity: a systematic review and meta-analysis. Sexually Transmitted Diseases 41, 369–376.Google Scholar
Stacey, KJ and Blackwell, JM (1999) Immunostimulatory DNA as an adjuvant in vaccination against Leishmania major. Infection and Immunity 67, 3719–3726.Google Scholar
Stacey, KJ, Sweet, MJ and Hume, DA (1996) Macrophages ingest and are activated by bacterial DNA. Journal of Immunology 157, 2116–2122.Google Scholar
Su, YW, Chiou, WF, Chao, SH, Lee, MH, Chen, CC and Tsai, YC (2011) Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-κB and AP-1 signaling pathways. International Immunopharmacology 11, 1166–1172.Google Scholar
Takeuchi, O and Akira, S (2010) Pattern recognition receptors and inflammation. Cell 140, 805–820.Google Scholar
Tan, HY, Wang, N, Li, S, Hong, M, Wang, X and Feng, Y (2016) The reactive oxygen species in macrophage polarization: reflecting its dual role in progression and treatment of human diseases. Oxidative Medicine and Cellular Longevity 2016, 2795090.Google Scholar
Warnatsch, A, Tsourouktsoglou, TD, Branzk, N, Wang, Q, Reincke, S, Herbst, S, Gutierrez, M and Papayannopoulos, V (2017) Reactive oxygen species localization programs inflammation to clear microbes of different size. Immunity 46, 421–432.Google Scholar
Zhu, Y, Fan, S, Wang, N, Chen, X, Yang, Y, Lu, Y, Chen, Q, Zheng, J and Liu, X (2017) NADPH oxidase 2 inhibitor diphenyleneiodonium enhances ROS-independent bacterial phagocytosis in murine macrophages via activation of the calcium-mediated p38 MAPK signaling pathway. American Journal of Translational Research 9, 3422–3432.Google Scholar
Zimmermann, S, Egeter, O, Hausmann, S, Lipford, GB, Röcken, M, Wagner, H and Heeg, K (1998) Cpg oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis. The Journal of Immunology 160, 3627–3630.Google Scholar
Zimmermann, S, Dalpke, A and Heeg, K (2008) Cpg oligonucleotides as adjuvant in therapeutic vaccines against parasitic infections. International Journal of Medical Microbiology 298, 39–44.Google Scholar
Supplementary material: File

Barajas-Mendiola et al. supplementary material

Tables S1-S2 and Figure S1

Download Barajas-Mendiola et al. supplementary material(File)
File 198.7 KB