Lytic Cycle of Toxoplasma gondii: 15 Years Later

Abstract

Toxoplasmosis is the clinical and pathological consequence of acute infection with the obligate intracellular apicomplexan parasite Toxoplasma gondii. Symptoms result from tissue destruction that accompanies lytic parasite growth. This review updates current understanding of the host cell invasion, parasite replication, and eventual egress that constitute the lytic cycle, as well as the ways T. gondii manipulates host cells to ensure its survival. Since the publication of a previous iteration of this review 15 years ago, important advances have been made in our molecular understanding of parasite growth and mechanisms of host cell egress, and knowledge of the parasite's manipulation of the host has rapidly progressed. Here we cover molecular advances and current conceptual frameworks that include each of these topics, with an eye to what may be known 15 years from now.

Keywords: Apicomplexa; IRG; egress; endodyogeny; inflammasome; invasion.

Figure 1

The Toxoplasma lytic cycle and basic tachyzoite organization. (a) The lytic cycle of invasion, replication and egress. (b) Organelles in the secretory pathway are shown in white; the actual secretory organelles in three hues of blue. PLV, plant like vacuole; EC endosome compartment; IMC, inner membrane complex; ER, endoplasmic reticulum.

Figure 2

Activation of egress, gliding motility and host cell invasion. (a) Schematic overview of described egress stimuli. The cytotoxic T-cell response (CTL) releases perforin inserting in the plasma membrane. Fas receptor activation induces host cell necrosis rather than apoptosis. Triangular insert: summary of Ca²⁺ and cGMP secondary messenger signaling following triggers to egress. (b) Invasion gliding motility and glideosome composition (modified from (53)); panel 1. Initial attachment and adhesion release. Panel 2. Molecular composition and mechanism of adhesion, gliding motility, the glideosome, and the moving junction. Not depicted is the family of actin binding proteins.

Figure 3

The cortical cytoskeleton and cell division. (a) A patchwork of alveoli (flattened vesicles) underlies the plasma membrane (left) which in turn are supported by a meshwork of intermediate filament-like IMC proteins (right). At the apical end (enlarged in center) the conoid composed of MT is an extrudable basket, whereas 22 cortical, subpellicular microtubules emanate from the apical end to about 2/3 the length of the parasite. At the basal end the cytoskeleton is capped by the basal complex and posterior cup, as magnified in panel 1. BIC, basal inner complex; BIR, basal inner ring. (b) Concurrent mitosis and cell division are coordinated by the centrosome. Mitosis is closed without chromosome condensation whereas the spindle resides eccentrically at the apical side of the nucleus. Throughout the cell cycle the 14 chromosomes are clustered at the centromeres and anchored at the spindle pole (centrocone) by the kinetochore. Daughter bud assembly starts before completion of mitosis and is driven by assembly of the cortical cytoskeleton in an apical to basal direction. The nucleus is anchored in the daughter scaffolds through the centrosome and SFA fiber. Constriction of the basal complex drives tapering of the daughter bud towards the basal end and is required to separate the daughter parasites. Magnification of black dotted regions next to relevant panel. Panel 2 magnifies the interaction between nucleus, centrosome and daughter cytoskeleton. SFA, striated fiber assemblin. Schematic modified from (62).