Skip to main content Accessibility help

Galectins expressed differently in genetically susceptible C57BL/6 and resistant BALB/c mice during acute ocular Toxoplasma gondii infection

  • S.-J. CHEN (a1) (a2), Y.-X. ZHANG (a1) (a2), S.-G. HUANG (a3) and F.-L. LU (a1) (a2)


Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin–receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.


Corresponding author

*Corresponding author: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China, Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, Guangdong, China and School of Stomatology, Jinan University, Guangzhou 510632, Guangdong, China. E-mail:;


Hide All
Anderson, A. C., Anderson, D. E., Bregoli, L., Hastings, W. D., Kassam, N., Lei, C., Chandwaskar, R., Karman, J., Su, E. W., Hirashima, M., Bruce, J. N., Kane, L. P., Kuchroo, V. K. and Hafler, D. A. (2007). Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 318, 11411143.
Argüeso, P., Guzman-Aranguez, A., Mantelli, F., Cao, Z., Ricciuto, J. and Panjwani, N. (2009). Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier. Journal of Biological Chemistry 284, 2303723045.
Baum, L. G., Garner, O. B., Schaefer, K. and Lee, B. (2014). Microbe-host interactions are positively and negatively regulated by galectin-glycan interactions. Frontiers in Immunology 5, 284.
Bernardes, E. S., Silva, N. M., Ruas, L. P., Mineo, J. R., Loyola, A. M., Hsu, D. K., Liu, F. T., Chammas, R. and Roque-Barreira, M. C. (2006). Toxoplasma gondii infection reveals a novel regulatory role for galectin-3 in the interface of innate and adaptive immunity. American Journal of Pathology 168, 19101920.
Buzoni–Gatel, D., Debbabi, H., Mennechet, F. J., Martin, V., Lepage, A. C., Schwartzman, J. D. and Kasper, L. H. (2001). Murine ileitis after intracellular parasite infection is controlled by TGF-β–producing intraepithelial lymphocytes. Gastroenterology 120, 914924.
Charles, E., Callegan, M. C. and Blader, I. J. (2007). The SAG1 Toxoplasma gondii surface protein is not required for acute ocular toxoplasmosis in mice. Infection and Immunity 75, 20792083.
Chiba, S., Baghdadi, M., Akiba, H., Yoshiyama, H., Kinoshita, I., Dosaka-Akita, H., Fujioka, Y., Ohba, Y., Gorman, J. V., Colgan, J. D., Hirashima, M., Uede, T., Takaoka, A., Yagita, H. and Jinushi, M. (2012). Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nature Immunology 13, 832842.
Deckert-Schlüter, M., Rang, A., Weiner, D., Huang, S., Wiestler, O. D., Hof, H. and Schlüter, D. (1996). Interferon-gamma receptor-deficiency renders mice highly susceptible to toxoplasmosis by decreased macrophage activation. Laboratory Investigation: a Journal of Technical Methods and Pathology 75, 827841.
Diez, B., Galdeano, A., Nicolas, R. and Cisterna, R. (1989). Relationship between the production of interferon-α/β and interferon-γ during acute toxoplasmosis. Parasitology 99, 1115.
Dukaczewska, A., Tedesco, R. and Liesenfeld, O. (2015). Experimental Models of Ocular Infection with Toxoplasma Gondii . European Journal of Microbiology & Immunology (Bp) 5, 293305.
Freshman, M. M., Merigan, T. C., Remington, J. S. and Brownlee, I. E. (1966). In vitro and in vivo antiviral action of an interferon-like substance induced by Toxoplasma gondii . Proceedings of the Society for Experimental Biology and Medicine 123, 862866.
Gazzinelli, R. T., Hakim, F. T., Hieny, S., Shearer, G. M. and Sher, A. (1991). Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. Journal of Immunology 146, 286292.
Gazzinelli, R., Xu, Y., Hieny, S., Cheever, A. and Sher, A. (1992). Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii . The Journal of Immunology 149, 175180.
Han, S. J., Melichar, H. J., Coombes, J. L., Chan, S. W., Koshy, A. A., Boothroyd, J. C., Barton, G. M. and Robey, E. A. (2014). Internalization and TLR-dependent type I interferon production by monocytes in response to Toxoplasma gondii . Immunology and Cell Biology 92, 872881.
Holland, G. N. (2003). Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease. American Journal of Ophthalmology 136, 973988.
Holland, G. N. (2004). Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. American Journal of Ophthalmology 137, 117.
Hu, X. H, Tang, M. X., Mor, G. and Liao, A. H. (2016). Tim-3: expression on immune cells and roles at the maternal-fetal interface. Journal of Reproductive Immunology 118, 9299.
Kojima, K., Arikawa, T., Saita, N., Goto, E., Tsumura, S., Tanaka, R., Masunaga, A., Niki, T., Oomizu, S. and Hirashima, M. (2011). Galectin-9 attenuates acute lung injury by expanding CD14–plasmacytoid dendritic cell-like macrophages. American Journal of Respiratory and Critical Care Medicine 184, 328339.
Kwon, B. S. and Weissman, S. M. (1989). cDNA sequences of two inducible T-cell genes. Proceedings of the National Academy of Sciences of the United States of America 86, 19631967.
Liang, S. and Qin, X. (2013). Critical role of type I interferon-induced macrophage necroptosis during infection with Salmonella enterica serovar Typhimurium. Cellular & Molecular Immunology 10, 99100.
Liesenfeld, O. (2002). Oral infection of C57BL/6 mice with Toxoplasma gondii: a new model of inflammatory bowel disease? Journal of Infectious Diseases 185 (Suppl. 1), S96101.
Liesenfeld, O., Kosek, J., Remington, J. S. and Suzuki, Y. (1996). Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii . Journal of Experimental Medicine 184, 597607.
Liu, F. T. and Rabinovich, G. A. (2010). Galectins: regulators of acute and chronic inflammation. Annals of the New York Academy of Sciences 1183, 158182.
Lu, F., Huang, S. and Kasper, L. H. (2003). Interleukin-10 and pathogenesis of murine ocular toxoplasmosis. Infection and Immunity 71, 71597163.
Lu, F., Huang, S., Hu, M. S. and Kasper, L. H. (2005). Experimental ocular toxoplasmosis in genetically susceptible and resistant mice. Infection and Immunity 73, 51605165.
Lu, X. X., McCoy, K. S., Xu, J. L., Hu, W. K., Chen, H. B., Jiang, K., Han, F., Chen, P. and Wang, Y. L. (2015). Galectin-9 ameliorates respiratory syncytial virus-induced pulmonary immunopathology through regulating the balance between Th17 and regulatory T cells. Virus Research 195, 162171.
Lückoff, A., Caramoy, A., Scholz, R., Prinz, M., Kalinke, U. and Langmann, T. (2016). Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization. EMBO Molecular Medicine 8, 670678.
Maenz, M., Schluter, D., Liesenfeld, O., Schares, G., Gross, U. and Pleyer, U. (2014). Ocular toxoplasmosis past, present and new aspects of an old disease. Progress in Retinal and Eye Research 39, 77106.
Nagineni, C. N., Pardhasaradhi, K., Martins, M. C., Detrick, B. and Hooks, J. J. (1996). Mechanisms of interferon-induced inhibition of Toxoplasma gondii replication in human retinal pigment epithelial cells. Infection and Immunity 64, 41884196.
Orellana, M. A., Suzuki, Y., Araujo, F. and Remington, J. S. (1991). Role of beta interferon in resistance to Toxoplasma gondii infection. Infection and Immunity 59, 32873290.
Panjwani, N. (2014). Role of galectins in re-epithelialization of wounds. Annals of Translational Medicine 2, 89.
Rochet, É., Brunet, J., Sabou, M., Marcellin, L., Bourcier, T., Candolfi, E. and Pfaff, A. W. (2015). Interleukin-6-driven inflammatory response induces retinal pathology in a model of ocular toxoplasmosis reactivation. Infection and Immunity 83 , 21092117.
Sadler, A. J. and Williams, B. R. (2008). Interferon-inducible antiviral effectors. Nature Reviews. Immunology 8, 559568.
Sampson, J. F., Hasegawa, E., Mulki, L., Suryawanshi, A., Jiang, S., Chen, W. S., Rabinovich, G. A., Connor, K. M. and Panjwani, N. (2015). Galectin-8 ameliorates murine autoimmune ocular pathology and promotes a regulatory T cell response. PLoS ONE 10, e0130772.
Sampson, J. F., Suryawanshi, A., Chen, W.-S., Rabinovich, G. A. and Panjwani, N. (2016). Galectin-8 promotes regulatory T-cell differentiation by modulating IL-2 and TGFβ signaling. Immunology and Cell Biology 94, 213219.
Sehrawat, S., Suryawanshi, A., Hirashima, M. and Rouse, B. T. (2009). Role of Tim-3/galectin-9 inhibitory interaction in viral-induced immunopathology: shifting the balance toward regulators. Journal of Immunology 182, 31913201.
Sehrawat, S., Reddy, P. B., Rajasagi, N., Suryawanshi, A., Hirashima, M. and Rouse, B. T. (2010). Galectin-9/TIM-3 interaction regulates virus-specific primary and memory CD8 T cell response. PLoS Pathogens 6, e1000882.
Sunil, V. R., Francis, M., Vayas, K. N., Cervelli, J. A., Choi, H., Laskin, J. D. and Laskin, D. L. (2015). Regulation of ozone-induced lung inflammation and injury by the beta-galactoside-binding lectin galectin-3. Toxicology and Applied Pharmacology 284, 236245.
Suryawanshi, A., Cao, Z., Thitiprasert, T., Zaidi, T. S. and Panjwani, N. (2013). Galectin-1-mediated suppression of Pseudomonas aeruginosa–induced corneal immunopathology. The Journal of Immunology 190, 63976409.
Suzuki, Y., Orellana, M. A., Schreiber, R. D. and Remington, J. S. (1988). Interferon-gamma: the major mediator of resistance against Toxoplasma gondii . Science 240, 516518.
Suzuki, Y., Yang, Q. and Remington, J. S. (1995). Genetic resistance against acute toxoplasmosis depends on the strain of Toxoplasma gondii . Journal of Parasitology 81, 10321034.
Vasta, G. R. (2009). Roles of galectins in infection. Nature Reviews Microbiology 7, 424438.
Viguier, M., Advedissian, T., Delacour, D., Poirier, F. and Deshayes, F. (2014). Galectins in epithelial functions. Tissue Barriers 2, e29103.
Wu, C., Thalhamer, T., Franca, R. F., Xiao, S., Wang, C., Hotta, C., Zhu, C., Hirashima, M., Anderson, A. C. and Kuchroo, V. K. (2014). Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells. Immunity 41, 270282.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed