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Effect of Toxoplasma gondii infection on the junctional complex of retinal pigment epithelial cells

  • ALANDERSON R. NOGUEIRA (a1), FERNANDA LEVE (a2), JOSÉ MORGADO-DIAZ (a2), ROBERTO CARLOS TEDESCO (a3) (a4) and MIRIAN CLAUDIA S. PEREIRA (a1)...
Summary

Ocular toxoplasmosis is the most frequent cause of uveitis, leading to partial or total loss of vision, with the retina the main affected structure. The cells of the retinal pigment epithelium (RPE) play an important role in the physiology of the retina and formation of the blood–retinal barrier. Several pathogens induce barrier dysfunction by altering tight junction (TJ) integrity. Here, we analysed the effect of infection by Toxoplasma gondii on TJ integrity in ARPE-19 cells. Loss of TJ integrity was demonstrated in T. gondii-infected ARPE-19 cells, causing increase in paracellular permeability and disturbance of the barrier function of the RPE. Confocal microscopy also revealed alteration in the TJ protein occludin induced by T. gondii infection. Disruption of junctional complex was also evidenced by scanning and transmission electron microscopy. Cell–cell contact loss was noticed in the early stages of infection by T. gondii with the visualization of small to moderate intercellular spaces. Large gaps were mostly observed with the progression of the infection. Thus, our data suggest that the alterations induced by T. gondii in the structural organization of the RPE may contribute to retinal injury evidenced by ocular toxoplasmosis.

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Corresponding author
*Corresponding author: Laboratório de Ultraestrutura Celular, Instituto Oswaldo Cruz, Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ 21040-900, Brazil. E-mail: mirian@ioc.fiocruz.br
References
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Bai, L., Zhang, Z., Zhang, H., Li, X., Yu, Q., Lin, H. and Yang, W. (2008). HIV-1 Tat protein alter the tight junction integrity and function of retinal pigment epithelium: an in vitro study. BMC Infectious Diseases 6, 877.
Ban, Y. and Rizzolo, L. J. (1997). A culture model of development reveals multiple properties of RPE tight junctions. Molecular Vision 31, 318. http://www.emory.edu/molvis/v3/ban.
Bauer, A. T., Bürgers, H. F., Rabie, T. and Marti, H. H. (2010). Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement. Cerebral Blood Flow and Metabolism 30, 837848.
Bissell, M. J. and Radisky, D. (2001). Putting tumours in context. Nature Reviews Cancer 1, 4654.
Campbell, M. and Humphries, P. (2012). The blood–retina barrier: tight junctions and barrier modulation. Advances in Experimental Medicine and Biology 763, 7084.
Commodaro, A. G., Belfort, R. N., Rizzo, L. V., Muccioli, C., Silveira, C., Burnier, M. N. Jr. and Belfort, R. Jr. (2009). Ocular toxoplasmosis: an update and review of the literature. Memórias do Instituto Oswaldo Cruz 104, 345350.
Contini, C. (2008). Clinical and diagnostic management of toxoplasmosis in the immunocompromised patient. Parasitologia 50, 4550.
Cunha-Vaz, J., Bernardes, R. and Lobo, C. (2011). Blood–retinal barrier. European Journal of Ophthalmology 21, S3S9.
Dalton, J. E., Cruickshank, S. M., Egan, C. E., Mears, R., Newton, D. J., Andrew, E. M., Lawrence, B., Howell, G., Else, K. J., Gubbels, M. J., Striepen, B., Smith, J. E., White, S. J. and Carding, S. R. (2006). Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 131, 818829.
Feng, S., Cen, J., Huang, Y., Shen, H., Yao, L., Wang, Y. and Chen, Z. (2011). Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase the permeability of blood-brain barrier by disrupting tight junction proteins. PLoS ONE 6, e20599.
Furtado, J. M., Bharadwaj, A. S., Ashander, L. M., Olivas, A. and Smith, J. R. (2012). Migration of Toxoplasma gondii-infected dendritic cells across human retinal vascular endothelium. Investigative Ophthalmology and Visual Science 53, 68566862.
Furtado, J. M., Ashander, L. M., Mohs, K., Chipps, T. J., Appukuttan, B. and Smith, J. R. (2013). Toxoplasma gondii migration within and infection of human retina. PLoS ONE 8, e54358.
Hamada, K., Kakigawa, N., Sekine, S., Shitara, Y. and Horie, T. (2013). Disruption of ZO-1/claudin-4 interaction in relation to inflammatory responses in methotrexate-induced intestinal mucositis. Cancer Chemotherapy and Pharmacology 72, 757765.
Haorah, J., Ramirez, S. H., Schall, K., Smith, D., Pandya, R. and Persidsky, Y. (2007). Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood-brain barrier dysfunction. Journal of Neurochemistry 101, 566576.
Holtkamp, G. M., Kijlstra, A., Peek, R. and de Vos, A. F. (2001). Retinal pigment epithelium-immune system interactions: cytokine production and cytokine-induced changes. Progress in Retinal and Eye Research 20, 2948.
Lu, R. Y., Yang, W. X. and Hu, Y. J. (2014). The role of epithelial tight junctions involved in pathogen infections. Molecular Biology Reports 10, 6591–610.
Mayhan, W. G. (2001). Regulation of blood–brain barrier permeability. Microcirculation 8, 89104.
Moyer, A. L., Ramadan, R. T., Novosad, B. D., Astley, R. and Callegan, M. C. (2009). Bacillus cereus-induced permeability of the blood-ocular barrier during experimental endophthalmitis. Investigative Ophthalmology and Visual Science 50, 37833793.
Nicholson, D. H. and Wolchok, E. B. (1976). Ocular toxoplasmosis in an adult receiving long-term corticosteroid therapy. Archives of Ophthalmology 94, 248254.
Ramadan, R. T., Ramirez, R., Novosad, B. D. and Callegan, M. C. (2006). Acute inflammation and loss of retinal architecture and function during experimental Bacillus endophthalmitis . Current Eye Research 31, 955965.
Rao, R. (2008). Oxidative stress-induced disruption of epithelial and endothelial tight junctions. Frontiers in Bioscience 13, 72107226.
Remington, J. S. and Desmonts, G. (1976). Toxoplasmosis. In Infections Diseases of the Fetus and Newborn Infant (ed. Remington, J. S. and Klein, J. O.), pp. 191332. Saunders, Philadelphia, PA, USA.
Rizzolo, L. J. (1997). Polarity and the development of the outer blood-retinal barrier. Histology and Histopathology 12, 10571067.
Rizzolo, L. J. (2014). Barrier properties of cultured retinal pigment epithelium. Experimental Eye Research 126, 1626.
Rizzolo, L. J., Peng, S., Luo, Y. and Xiao, W. (2011). Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium. Progress in Retinal and Eye Research 30, 296323.
Robert-Gangneux, F. and Dardé, M. L. (2012). Epidemiology of and diagnostic strategies for toxoplasmosis. Clinical Microbiology Reviews 25, 264296. Erratum in: Clinical Microbiology Reviews 25, 583.
Rothova, A., Meenken, C., Buitenhuis, H. J., Brinkman, C. J., Baarsma, G. S., Boen-Tan, T. N., de Jong, P. T., Klaassen-Broekema, N., Schweitzer, C. M., Timmerman, Z., de Vries, J., Zaal, M. J. W. and Kijlstra, A. (1993). Therapy for ocular toxoplasmosis. American Journal of Ophthalmology 115, 517523.
Stanford, M. R., Tomlin, E. A., Comyn, O., Holland, K. and Pavesio, C. (2005). The visual field in toxoplasmic retinochoroiditis. British Journal of Ophthalmology 89, 812814.
Shin, K., Fogg, V. C. and Margolis, B. (2006). Tight junctions and cell polarity. Annual Review of Cell and Developmental Biology 22, 207235.
Stein-Streilein, J. (2008). Immune regulation and the eye. Trends in Immunology 29, 548554.
Stein-Streilein, J. (2013). Mechanisms of immune privilege in the posterior eye. International Reviews of Immunology 32, 4256.
Sugita, S. (2009). Role of ocular pigment epithelial cells in immune privilege. Archivum Immunologiae et Therapia Experimentalis 57, 263268.
Talabani, H., Mergey, T., Year, H., Delair, E., Brézin, A. P., Langsley, G. and Dupouy-Camet, J. (2010). Factors of occurrence of ocular toxoplasmosis. A review. Parasite 17, 177182.
Tedesco, R. C., Smith, R. L., Corte-Real, S. and Calabrese, K. S. (2004). Ocular toxoplasmosis: the role of retinal pigment epithelium migration in infection. Parasitology Research 92, 467472.
Vallochi, A. L., Nakamura, M. V., Schlesinger, D., Martins, M. C., Silveira, C., Belfort, R. Jr. and Rizzo, L. V. (2002). Ocular toxoplasmosis: more than just what meets the eye. Scandinavian Journal of Immunology 55, 324328.
Wang, M. F. and Lai, S. C. (2013). Fibronectin degradation by MMP-2/MMP-9 in the serum of pregnant women and umbilical cord with Toxoplasma gondii infection. Journal of Obstetrics and Gynaecology 33, 370374.
Wenkel, H. and Streilein, J. W. (1998). Analysis of immune deviation elicited by antigens injected into the subretinal space. Investigative Ophthalmology and Visual Science 39, 18231834.
Willermain, F., Caspers-Velu, L., Nowak, B., Stordeur, P., Mosselmans, R., Salmon, I., Velu, T. and Bruyns, C. (2002). Retinal pigment epithelial cells phagocytosis of T lymphocytes: possible implication in the immune privilege of the eye. British Journal of Ophthalmology 86, 14171421.
Zhang, C. O., Wang, J. Y., Koch, K. R. and Keay, S. (2005). Regulation of tight junction proteins and bladder epithelial paracellular permeability by an antiproliferative factor from patients with interstitial cystitis. Journal of Urology 174, 23822387.
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Parasitology
  • ISSN: 0031-1820
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