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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
Abstract:
Little is known about signalling in Toxoplasma gondii, but it is likely that protein kinases might play a key role in the parasite proliferation, differentiation and probably invasion. We previously characterized Mitogen-Activated Protein (MAP) kinases in T. gondii lysates. In this study, cultured cells were tested for their susceptibility to Toxoplasma gondii infection after tachyzoite pretreatment with drugs interfering with MAP kinase activation pathways. Protein kinases inhibitors, i.e. genistein, RO31-8220 and PD098059, reduced tachyzoite infectivity by 38 +/- 4.5%, 85.5 +/- 9% and 56 +/- 10%, respectively. Conversely, protein kinases activators, i.e. bombesin and PMA, markedly increased infectivity (by 202 +/- 37% and 258 +/- 14%, respectively). These results suggest that signalling pathways involving PKC and MAP kinases play a role in host cell invasion by Toxoplasma.
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.