Skip to main content

Advertisement

Log in

Endothelial cell invasion by Toxoplasma gondii: differences between cell types and parasite strains

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Toxoplasma gondii disseminates and causes congenital infection by invasion of the endothelial cells. The aim of this study was to analyze the ability of two strains to invade two endothelial cell types. Tachyzoites of the RH and ME49 strains were expanded in Balb/c and C57BL6-RAG2−/− mice, respectively. Tachyzoites were harvested from 72 h Vero cell cultures and incubated for 30 min to 4 h at 10:1 parasite/cell ratio in 24-well plates, containing monolayers of either HMEC-1 line or human umbilical cells (HUVECs). The number of infected cells and parasitic vacuoles per infected cell were counted in Wright stained slides. A slow increase in the proportion of infected cells occurred but varied according to cell type–parasite strain combination: ME49 tachyzoites invaded up to 63 % HMEC-1 cells, while RH parasites infected up to 19 % HUVECs. ME49 and RH tachyzoites invaded 49 and 46 % HUVECs and HMEC-1 cells, respectively. Reinvasion and formation of new parasitophorous vacuoles of infected cells was more frequent than invasion of noninfected cells. The results support that the factors influencing invasion, and thus dissemination and vertical transmission, are parasite type, host cell type/subtype, and activation state. Interestingly, T. gondii virulence does not seem to relay on its invasion efficiency, but probably on replication speed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abou-Bacar A, Pfaff AW, Letscher-Bru V, Filisetti D, Rajapakse R, Antoni E, Villard O, Klein JP, Candolfi E (2004) Role of gamma interferon and T cells in congenital Toxoplasma transmission. Parasite Immunol 26:315–318

    Article  PubMed  CAS  Google Scholar 

  • Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ (1992) HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol 99:683–690

    Article  PubMed  CAS  Google Scholar 

  • Angeloni MB, Silva NM, Castro AS, Gomes AO, Silva DA, Mineo JR, Ferro EA (2009) Apoptosis and S phase of the cell cycle in BeWo trophoblastic and HeLa cells are differentially modulated by Toxoplasma gondii strain types. Placenta 30:785–791

    Article  PubMed  CAS  Google Scholar 

  • Barragán A, Brossier F, Sibley LD (2005) Transepithelial migration of Toxoplasma gondii involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite adhesin MIC2. Cell Microbiol 7:561–568

    Article  PubMed  Google Scholar 

  • Benedetto N, Folgore A, Ferrara C, Molitierno M, Galdiero F (1997) Effects of alpha-adrenergic agonists on Toxoplasma gondii replication in human umbilical vein endothelial cells. Pathol Biol 45:9–18

    PubMed  CAS  Google Scholar 

  • Bonnefoy A, Harsfalvi J, Pfliegler G, Fauvel-Lafève F, Legrand C (2001) The sub endothelium of the HMEC-1 cell line supports thrombus formation in the absence of von Willebrand factor and collagen types I, III, and VI. Thromb Haemost 85:552–559

    PubMed  CAS  Google Scholar 

  • Bouïs D, Hospers GA, Meijer C, Molema G, Mulder NH (2001) Endothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis 4:91–102

    Article  PubMed  Google Scholar 

  • 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 107:245–249

    Article  PubMed  CAS  Google Scholar 

  • Carruthers V, Boothroyd JC (2007) Pulling together: an integrated model of Toxoplasma cell invasion. Curr Opin Microbiol 10:83–89

    Article  PubMed  CAS  Google Scholar 

  • Contreras-Ochoa CO, Laguna-Martínez A, Belkind-Gerson J, Correa D (2012) Toxoplasma gondii invasion and replication in astrocyte primary cultures and astrocytoma cell lines: systematic review of the literature. Parasitol Res 110:2089–2094

    Article  PubMed  Google Scholar 

  • Contreras-Ochoa CO, Lagunas-Martínez A, Belkind-Gerson J, Díaz-Chávez J, Correa D (2013) Toxoplasma gondii invasion and replication within neonate mouse astrocytes and changes in apoptosis related molecules. Exp Parasitol 134:256–265

    Article  PubMed  CAS  Google Scholar 

  • Cortez E, Stumbo AC, de Carvalho TM, Barbosa HS, Carvalho L (2005) NAD(P)H-oxidase presence in Toxoplasma gondii tachyzoite vacuole during interaction with IFN-gamma-activated human endothelial cells. J Parasitol 91:1052–1057

    Article  PubMed  CAS  Google Scholar 

  • Dimer IH, Bout DT (1996) Inhibitory effect of interferon gamma-activated ovine umbilical vein endothelial cells on the intracellular replication of Toxoplasma gondii. Vet Res 27:527–534

    Google Scholar 

  • Dimier IH, Bout DT (1993) Cooperation of interleukin-1b and tumor necrosis factor-a in the activation of human umbilical vein endothelial cells to inhibit Toxoplasma gondii replication. Immunology 79:336–338

    PubMed  CAS  Google Scholar 

  • Dubey JP (2010) Toxoplasmosis of animals and humans. CRC Press, Florida

    Google Scholar 

  • Elsheikha HM (2008) Congenital toxoplasmosis: priorities for further health promotion action. Public Health 22:335–353

    Article  Google Scholar 

  • Kafsack BFC, Pena JDO, Coppens I, Ravindran S, Boothroyd JC, Carruthers VB (2009) Rapid membrane disruption by a perforin-like protein facilitates parasite exit from hist cells. Science 323:530–533

    Article  PubMed  CAS  Google Scholar 

  • Lachenmaier SM, Deli MA, Meissner M, Liesenfeld O (2011) Intracellular transport of Toxoplasma gondii through the blood–brain barrier. J Neuroimmunol 232:119–130

    Article  PubMed  CAS  Google Scholar 

  • Lavine MD, Arrizabalaga G (2009) Induction of mitotic S-phase of host and neighboring cells by Toxoplasma gondii enhances parasite invasion. Mol. Biochem Parasitol 64:95–99

    Article  Google Scholar 

  • Ortiz-Alegría LB, Caballero-Ortega H, Cañedo-Solares I, Rico-Torres CP, Sahagún-Ruiz A, Medina–Escutia ME, Correa D (2010) Congenital toxoplasmosis: the role of host and parasite genetics on transmission and pathogenesis. Genes Immun 11:363–373

    Article  PubMed  Google Scholar 

  • Paez A, Mendez-Cruz AR, Varela E, Rodriguez E, Guevara J, Flores-Romo L, Montaño LF, Massó FA (2005) HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents. Clin Exp Immunol 141:449–458

    Article  PubMed  CAS  Google Scholar 

  • Pauly RR, Passaniti A, Crow M, Kinsella JL, Papadopoulos N, Monticone R, Lakatta EG, Martin GR (1992) Experimental models that mimic the differentiation and dedifferentiation of vascular cells. Circulation 86:68–73

    Google Scholar 

  • Radke JR, Striepen B, Guerini MN, Jerome ME, Roos DS, White MW (2001) Defining the cell cycle for the tachyzoite stage of Toxoplasma gondii. Mol Biochem Parasitol 115:165–175

    Article  PubMed  CAS  Google Scholar 

  • Radke JR, White MW (1998) A cell cycle model for the tachyzoite of Toxoplasma gondii using the herpes simplex virus thymidine kinase. Mol Biochem Parasitol 94:237–247

    Article  PubMed  CAS  Google Scholar 

  • Saeij JP, Boyle JP, Grigg ME, Arrizabalaga G, Boothroyd JC (2005) Bioluminescence imaging of Toxoplasma gondii infection in living mice reveals dramatic differences between strains. Infect Immun 73:695–702

    Article  PubMed  CAS  Google Scholar 

  • Smith JR, Franc DT, Carter NS, Zamora D, Planck SR, Rosenbaum JT (2004) Susceptibility of retinal vascular endothelium to infection with Toxoplasma gondii tachyzoites. Invest Ophthalmol Vis Sci 45:1157–1161

    Article  PubMed  Google Scholar 

  • Unger RE, Konvalinkova VK, Peters K, Kirkpatrick CJ (2002) In vitro expression of the endothelial phenotype: comparative study of primary isolated cells and cell lines, including the novel cell line HPMEC-ST1.6R. Microvasc Res 64:384–397

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Swerlick RA, Sepp N, Bosse D, Ades EW, Lawley TJ (1994) Characterization of expression and modulation of cell adhesion molecules on an immortalized human dermal microvascular endothelial cell line (HMEC-1). J Invest Dermatol 102:833–837

    Article  PubMed  CAS  Google Scholar 

  • Youn JH, Nam HW, Kim DJ, Park YM, Kim WK, Kim WS, Choi WY (1991) Cell cycle-dependent entry of Toxoplasma gondii into synchronized HL-60 cells. Korean. J Parasitol 29:121–128

    CAS  Google Scholar 

  • Zamora DO, Rosenbaum JT, Smith JR (2008) Invasion of human retinal vascular endothelial cells by Toxoplasma gondii tachyzoites. Br J Ophthalmol 92:852–855

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are in debt to Dr. Felipe A. Massó and Dr. Araceli Páez for their invaluable advice and support in the collection of cords and the in vitro culture of HUVECs, to Dr. Guadalupe Santiago-Ramos for cord collection and donation, and to Héctor Luna-Pastén and Rafael López-Reboseño for technical assistance in tachyzoite reproduction in mice. This work was supported by the National Council of Science and Technology of Mexico (CONACyT, grant number 139721).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dolores Correa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cañedo-Solares, I., Calzada-Ruiz, M., Ortiz-Alegría, L.B. et al. Endothelial cell invasion by Toxoplasma gondii: differences between cell types and parasite strains. Parasitol Res 112, 3029–3033 (2013). https://doi.org/10.1007/s00436-013-3476-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-013-3476-2

Keywords

Navigation