Involvement of the mitogen-activated protein (MAP) kinase signalling pathway in host cell invasion by Toxoplasma

F Robert-Gangneux1, C Creuzet, J Dupouy-Camet

  • 1Laboratoire Signalisation et Parasites, Université Paris 5, Centre Hospitalier Universitaire Cochin-Port Royal, Paris, France. florence.gangneux-robert@cch.ap-hop-paris.fr

Parasite (Paris, France)
|July 11, 2000
PubMed

Insights

Signalling pathways involving protein kinases, specifically Mitogen-Activated Protein (MAP) kinases and Protein Kinase C (PKC), are crucial for Toxoplasma gondii invasion. Inhibiting these pathways reduces parasite infectivity, while activating them increases it.

Area of Science:

  • Parasitology
  • Cell Biology
  • Molecular Biology

Background:

  • Signalling pathways in *Toxoplasma gondii* remain largely uncharacterized.
  • Protein kinases are hypothesized to regulate parasite proliferation, differentiation, and invasion.
  • Previous work identified Mitogen-Activated Protein (MAP) kinases in *T. gondii* lysates.

Purpose of the Study:

  • To investigate the role of signalling pathways, particularly those involving MAP kinases and Protein Kinase C (PKC), in *Toxoplasma gondii* host cell invasion.
  • To assess the impact of modulating these pathways on parasite infectivity.

Main Methods:

  • Cultured cells were infected with *Toxoplasma gondii* tachyzoites.
  • Tachyzoites were pretreated with specific protein kinase inhibitors (genistein, RO31-8220, PD098059) and activators (bombesin, PMA).
  • Parasite infectivity was quantified by measuring the susceptibility of host cells to infection.

Main Results:

  • Protein kinase inhibitors significantly reduced *T. gondii* tachyzoite infectivity: genistein (38 +/- 4.5%), RO31-8220 (85.5 +/- 9%), and PD098059 (56 +/- 10%).
  • Protein kinase activators markedly increased infectivity: bombesin (202 +/- 37%) and PMA (258 +/- 14%).

Conclusions:

  • Signalling pathways involving MAP kinases and PKC are critical for *Toxoplasma gondii* invasion into host cells.
  • Modulation of these kinase pathways directly affects the parasite's ability to infect host cells.
  • These findings provide insights into the molecular mechanisms of *T. gondii* pathogenesis.

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