Parasitology Research

, Volume 110, Issue 6, pp 2089–2094 | Cite as

Toxoplasma gondii invasion and replication in astrocyte primary cultures and astrocytoma cell lines: systematic review of the literature

  • Carla O. Contreras-Ochoa
  • Alfredo Lagunas-Martínez
  • Jaime Belkind-Gerson
  • Dolores CorreaEmail author


Toxoplasma gondii is a cosmopolitan protozoan which infects all homoeothermic species, including humans. This parasite may cause severe neurological problems in congenitally infected newborns or immunocompromised individuals, but it also provokes psychiatric and neurological disorders as well as behavioural and sensory deficit. There is controversy regarding the effect of T. gondii upon astrocytes, which may serve as parasite proliferation recipients or protective immune response activators within the central nervous system. This apparent contradiction could partially be due to the infection degree obtained in the different experiments reported. Thus, we decided to systematically review the in vitro models used to study these phenomena. Fifteen articles from which direct invasion and replication data could be gathered were found. Very heterogeneous results emerged, mainly due to diversity of models in relation to parasite strain (virulence), host species, parasite dose and evaluation times after infection. Also, the results were measured in diverse ways, i.e. some reported percent infected cells, while others informed parasites per vacuole or cell, or parasitic vacuoles per cell. Very few conclusions could be drawn, among them that human astrocytoma cell lines and mouse astrocytes seem more susceptible to infection and less resistant to tachyzoite proliferation than human primary culture astrocytes. The present study supports the need to reanalyse T. gondii astrocyte invasion and replication processes, especially with the use of actual technology, which allows detailed mechanistic studies.


Astrocytoma Toxoplasmosis Parasitophorous Vacuole Toxoplasmic Encephalitis Astrocyte Primary Culture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Berdoy M, Webster J, Macdonald D (2000) Fatal attraction in rats infected with Toxoplasma gondii. Proc Biol Sci 267:1591–1594PubMedCrossRefGoogle Scholar
  2. Boyle JP, Radke JR (2009) A history of studies that examine the interactions of Toxoplasma with its host cell emphasis on in vitro models. Int J Parasitol 39:903–914PubMedCrossRefGoogle Scholar
  3. Brenier-Pinchart MP, Blanc-Gonnet E, Marche PN, Berger F, Durand F, Ambroise-Thomas P, Pelloux H (2004) Infection of human astrocytes and glioblastoma cells with Toxoplasma gondii: monocyte chemotactic protein 1 secretion and chemokine expression in vitro. Acta Neuropathol 107:245–249PubMedCrossRefGoogle Scholar
  4. Carruthers VB, Suzuki Y (2007) Effects of Toxoplasma gondii infection on the brain. Schizophr Bull 33:745–751PubMedCrossRefGoogle Scholar
  5. Creuzet C, Robert F, Roisin MP, Van Tan H, Benes C, Dupouy-Camet FR (1998) Neurons in primary culture are less efficiently infected by Toxoplasma gondii than glial cells. Parasitol Res 84:25–30PubMedCrossRefGoogle Scholar
  6. Däubener W, Pilz K, Seghrouchni-Zennati S, Bilzer T, Fischer HG, Hadding U (1993) Induction of toxoplasmostasis in a human glioblastoma by interferon gamma. J Neuroimmunol 43:31–38PubMedCrossRefGoogle Scholar
  7. Däubener W, Remscheid C, Nockemann S, Pilz K, Seghrouchni S, Mackenzie C, Seghrouchni S, Hadding U (1996) Anti-parasitic effector mechanisms in human brain tumor cells: role of interferon-gamma and tumor necrosis factor-alpha. Eur J Immunol 26:487–492PubMedCrossRefGoogle Scholar
  8. el-Sagaff S, Salem HS, Nichols W, Tonkel AK, Abo-Zenadah NY (2005) Cell death pattern in cerebellum neurons infected with Toxoplasma gondii. J Egypt Soc Parasitol 35:809–818PubMedGoogle Scholar
  9. Estran C, Brenier-Pinchart MP, Pelletier L, Cesbron-Delauw MF, Pelloux H (2006) Toxoplasma gondii in human astrocytes in vitro: interleukin (IL)-12 and IL-10 do not influence cystogenesis. J Parasitol 92:1108–1110PubMedCrossRefGoogle Scholar
  10. Fagard R, Van Tan H, Creuzet C, Pelloux H (1999) Differential development of Toxoplasma gondii in neural cells. Parasitol Today 15:504–507PubMedCrossRefGoogle Scholar
  11. Fischer HG, Nitzgen B, Reichmann G, Gross U, Hadding U (1997a) Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells. Eur J Immunol 27:1539–1548PubMedCrossRefGoogle Scholar
  12. Fischer HG, Nitzgen B, Reichmann G, Gross U, Hadding U (1997b) Host cells of Toxoplasma gondii encystation in infected primary culture from mouse brain. Parasitol Res 83:637–641PubMedCrossRefGoogle Scholar
  13. Flegr J, Kodym P, Tolarova V (2000) Correlation of duration of latent Toxoplasma gondii infection with personality changes in women. Biol Psychol 53:57–68PubMedCrossRefGoogle Scholar
  14. Giaume C, Kirchhoff F, Matute C, Reichenbach A, Verkhratsky A (2007) Glia: the fulcrum of brain diseases. Cell Death Differ 14:1324–1335PubMedCrossRefGoogle Scholar
  15. Gulinello M, Acquarone M, Kim JH, Spray DC, Barbosa HS, Sellers R, Tanowitz HB, Weiss LM (2010) Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. Microbes Infect 12:528–537PubMedCrossRefGoogle Scholar
  16. Halonen SK, Weiss LM (2000) Investigation into the mechanism of gamma interferon-mediated inhibition of Toxoplasma gondii in murine astrocytes. Infect Immun 68:3426–3430PubMedCrossRefGoogle Scholar
  17. Halonen SK, Lyman WD, Chiu FC (1996) Growth and development of Toxoplasma gondii in human neurons and astrocytes. J Neuropathol Exp Neurol 55:1150–1156PubMedCrossRefGoogle Scholar
  18. Halonen SK, Chiu F, Weiss LM (1998) Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes. Infect Immun 66:4989–4993PubMedGoogle Scholar
  19. Hamidinejat H, Ghorbanpoor M, Hosseini H, Alavi SM, Nabavi L, Jalali MH, Borojeni MP, Jafari H, Mohammadaligol S (2010) Toxoplasma gondii infection in first-episode and patient individuals with schizophrenia. Int J Infect Dis 14:978–981CrossRefGoogle Scholar
  20. Jones J, Lopez A, Wilson M (2003) Congenital toxoplasmosis. Am Fam Physician 67:2131–2138PubMedGoogle Scholar
  21. Lüder CGK, Giraldo-Velásquez M, Sendtner M, Gross U (1999) Toxoplasma gondii in primary rat CNS cells: differential contribution of neurons, astrocytes, and microglial cells for the intracerebral development and stage differentiation. Exp Parasitol 93:23–32PubMedCrossRefGoogle Scholar
  22. Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, Reichmann G, Howard JC (2005) Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47 resistance GTPases. PLoS Pathog 1:24–30CrossRefGoogle Scholar
  23. Melzer T, Duffy A, Weiss LM, Halonen SK (2008) The gamma interferon (IFN-gamma) inducible GTP-binding protein IGTP is necessary for toxoplasma vacuolar disruption and induces parasite egression in IFN-gamma-stimulated astrocytes. Infect Immun 76:4883–4894PubMedCrossRefGoogle Scholar
  24. Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363:1965–1976PubMedCrossRefGoogle Scholar
  25. Pelloux H, Ricard J, Nissou MF, Renversez JC, Vuillez JP, Meunier A, Ambroise-Thomas P (1994) Infection with Toxoplasma gondii does not alter TNF-α and IL-6 secretion by a human astrocytoma cell line. Mediators Inflamm 3:291–295PubMedCrossRefGoogle Scholar
  26. Pelloux H, Pernod G, Polack B, Coursange E, Ricard J, Verna JM, Ambroise-Thomas P (1996) Influence of cytokines on Toxoplasma gondii growth in human astrocytoma-derived cells. Parasitol Res 82:598–603PubMedCrossRefGoogle Scholar
  27. Peterson PK, Gekker G, Hu S, Chao C (1993) Intracellular survival and multiplication of Toxoplasma gondii in astrocytes. J Infect Dis 168:1472–1478PubMedCrossRefGoogle Scholar
  28. Peterson PK, Gekker G, Hu S, Chao CC (1995) Human astrocytes inhibit intracellular multiplication of Toxoplasma gondii by a nitric oxide-mediated mechanism. J Infect Dis 171:516–518PubMedCrossRefGoogle Scholar
  29. Shen DF, Matteson DM, Tuaillon N, Suedekum BK, Buggage RR, Chan CC (2001) Involvement of apoptosis and interferon-gamma in murine toxoplasmosis. Invest Ophthalmol Vis Sci 42:2031–2036PubMedGoogle Scholar
  30. Skallová A, Kodym P, Frynta D, Flegr J (2006) The role of dopamine in Toxoplasma-induced behavioural alterations in mice: an ethological and ethopharmacological study. Parasitology 133:525–535PubMedCrossRefGoogle Scholar
  31. Strack A, Asensio VC, Campbell IL, Schlüter D, Deckert M (2002) Chemokines are differentially expressed by astrocytes, microglia and inflammatory leukocytes in Toxoplasma encephalitis and critically regulated by interferon-gamma. Acta Neuropathol 103:458–468PubMedCrossRefGoogle Scholar
  32. Takahashi J, Fukuda T, Tanaka J, Minamitani M, Onouchi K, Makioka A (2001) Bax-induced apoptosis not demonstrated in the congenital toxoplasmosis in mice. Brain Dev 23:50–53PubMedCrossRefGoogle Scholar
  33. Troyo A, Chinchilla M (2003) In vitro multiplication of Toxoplasma gondii and Trypanosoma cruzi in mouse, rat and hamster astrocytes. Rev Biol Trop 51:639–645PubMedGoogle Scholar
  34. Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626–640PubMedCrossRefGoogle Scholar
  35. Vyas A, Kim SK, Giacomini N, Boothroyd JC, Sapolsky RM (2007) Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc Natl Acad Sci U S A 104:6442–6447PubMedCrossRefGoogle Scholar
  36. Webster JP, McConkey GA (2010) Toxoplasma gondii-altered host behaviour: clues as to mechanism of action. Folia Parasitol (Praha) 57:95–104Google Scholar
  37. Wilson EH, Hunter CA (2004) The role of astrocytes in the immunopathogenesis toxoplasmic encephalitis. Int J Parasitol 34:543–548PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Carla O. Contreras-Ochoa
    • 1
    • 2
    • 3
  • Alfredo Lagunas-Martínez
    • 1
  • Jaime Belkind-Gerson
    • 2
  • Dolores Correa
    • 3
    Email author
  1. 1.Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud PúblicaCuernavacaMexico
  2. 2.Laboratorio de Medicina Regenerativa, Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud PúblicaCuernavacaMexico
  3. 3.Laboratorio de Inmunología Experimental, Instituto Nacional de PediatríaMexico DFMexico

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