NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013.

Cover of Madame Curie Bioscience Database

Madame Curie Bioscience Database [Internet].

Show details

Invasion and Intracellular Survival by Toxoplasma

, , , and .

Author Information

Summary

Toxoplasma gondii infects a wide range of warm-blooded vertebrates including humans and is one of the world's most successful parasites. As a member of the phylum Apicomplexa, T. gondii is a model for understanding infection by a variety of related parasites such as Plasmodium and Cryptosporidium. Apicomplexans use a unique form of actin-based motility to directly penetrate their host cell, without the need for host uptake mechanisms. Invasion occurs more rapidly than phagocytic uptake and avoids triggering of the respiratory burst in macrophages. Within the host cell, the parasite resides in a modified vacuole that resists fusion with endosomes and lysosomes, while intimately associate with host cell ER and mitochondria. Active secretion of parasite proteins results in modification of the vacuole, rendering it permeable to small molecules. Within this porous vacuole the parasite acquires nutrients from the host cytosol, allowing rapid replication, and eventual consumption of the host cell prior to egress. Understanding the complex biology of intracellular survival by T. gondii has bearing on the mechanisms of host resistance during both acute and chronic infection.

Life Cycle and Basic Biology

The phylum Apicomplexa contains some 5,000 members, most of which are parasitic, although only a few of these have been studied.1 Apicomplexans are unified by an apical complex consisting of a unique microtubule organizing center called the conoid, and a system of apical secretory organelles involved in cell invasion.2 A number of apicomplexans are important pathogens in humans (e.g., Plasmodium spp., Cryptosporidium spp., T. gondii) or in animals (e.g., Eimeria spp. Neospora caninum, Sarcocystis spp.). Apicomplexans are early branching eukaryotes and are most closely related to ciliates and dinoflagellates.3 Consequently, their basic cellular mechanisms are often unlike those of their host cells. Toxoplasma gondii is equipped with forward and reverse genetics, excellent animals models, and is amenable to cell biological and biochemical analyses,4 and thus it provides an ideal model organism for studying the unique biology of this phylum.

Toxoplasma gondii is a generalist both in its host range and choice of cell type. Virtually all warm-blooded vertebrates are susceptible hosts5 and within its host, all nucleated cells are subject to infection. T. gondii is adept at entering and surviving in a variety of leukocytes and both monocytes and dendritic cells are highly permissive for replication.6 Early studies established that T. gondii enters macrophages without stimulating a respiratory burst.7 The parasite establishes a vacuole that resist fusion with endosomes and lysosomes8,9 and which maintain a neutral pH.10 Avoidance of acidification and endosome fusion relies on active penetration of the cell and when parasites are opsonized by specific antibody and engulfed via Fc receptors they rapidly fuse and acidify.10,11 These observations led to the suggestion that parasite invasion was an active process and more recent molecular studies have validated this hypothesis (discussed further below).

T. gondii has a complex life cycle consisting of haploid replicating stages that infect a variety of intermediate hosts and meiosis following infection of felines, which are the only known definite host.12 Transmission of T. gondii occurs by one of two routes: ingestion of oocysts that are shed in the feces from infected cats or ingestion of tissue cysts contained within undercooked meat. Direct infectivity of tissue cysts (containing bradyzoites) to other intermediate host is a unique feature in the life cycle of T. gondii, as all related parasites have a strictly obligatory two-host cycle. Following oral ingestion, sporozoites (contained within oocysts) or bradyzoites (contained within tissue cysts) emerge and penetrate epithelial cells of the small intestine. Herein they may develop, or may pass across the intestinal barrier to reach deeper tissues. When infection commences in the cat gut, haploid replication (schizogony) is followed by differentiation into gametocytes, which ultimately fuse to form a zygote and develop into an oocyst. When infection occurs in all other hosts, the parasite undergoes conversion to fast growing, lytic form called the tachyzoite, which is responsible for dissemination throughout the host. Replication of tachyzoites is ultimately curtailed by the innate and adaptive immune systems (dealt with elsewhere in this volume). Throughout these different developmental phases and within different tissues, T. gondii remains an obligate intracellular parasite.

Actin-Based Motility and Cell Invasion

Apicomplexan parasites are equipped with a unique form of motility termed gliding.13 Motility is strictly substrate dependent and occurs in the absence of cilia, flagella, or crawling behaviors exhibited by amoeboid cells. Instead, forward propulsion relies on a continuous conveyor belt of adhesive proteins attached the substrate.14 Reward translocation of these adhesin-substrate complexes is governed by an actin-dependent myosin motor beneath the plasma membrane.14 Gliding propels the parasite forward at 1-2 microns per second15 and also powers cell invasion and enables migration across cellular barriers.16,17 Gliding motility is conserved in a variety of apicomplexan parasites including very early branching members such as Cryptosporidium spp.18 and Gregarines.19 Cryptosporidium occupies a vacuole that remains at the apical surface of enterocytes.20 While this compartment is modified by an underlying actin-rich pedestal that forms in the host cell cytosol, the initial mode of entry is based on actin-based motility by the parasite, similar to Toxoplasma.21

Treatment with cytochalasins, which disrupt actin filaments, impairs entry of T. gondii22 and P. falciparum23 into their respective host cells. Cytochalasins block parasite gliding and host phagocytic responses, thus confounding the interpretation of the observed inhibition of invasion. Conclusive demonstration that parasite actin filaments are essential for host cell invasion was provided by mutational analysis and molecular genetic studies in T. gondii.24 In contrast, there are no discernable changes in the host cytoskeleton during invasion25 and the host cytoskeletal system appears to be nonessential to the process of entry. This active mode of cell invasion is distinct from mechanism used by bacterial and viral pathogens and is likely conserved among other members of the Apicomplexa.

Actin filaments are extremely dynamic in parasites and rapid turnover of filaments in likely important for regulating motility.26 Formation of new filaments appears to be rate limiting for motility.26 The motor force for motility is provided by a small myosin anchored as part of a complex in the inner membrane complex.27 Disruption of the gene encoding this myosin (TgMyoA) results in parasite that are nonmotile and unable to invade cells.28 The cytoplasmic tails of adhesins mediate connection between this motor complex and proteins that span the plasma membrane. The C terminal cytoplasmic domain of MIC2 contains a cluster of conserved acidic residues and a penultimate W residue, features that are shared by other microneme proteins in T. gondii and Plasmodium.29 Interaction between the C terminal domain of MIC2 and aldolase has been shown to bridge the interaction to the cytoskeleton.30 A similar interaction occurs between the Plasmodium adhesin known as TRAP, which is essential for gliding and invasion by sporozoites.31 Mutation of the key W residue disrupts aldolase binding and renders parasite nonmotile and noninvasive.30,32,33

The process of gliding motility requires the coordinated activities of protein secretion and translocation via the actin-based cytoskeleton. Adhesion to the cell substrate and host cell receptors is largely mediated by microneme proteins,34 which are discharged apically from small secretory vesicles. MIC secretion is a calcium regulated process that occurs constitutively and which is upregulated on contact with host cells.35 Apical discharge assures polarization and consistent with this gliding only occurs in a directional manner with the parasite moving forward along the substrate.15 Apically discharged adhesins form contacts with the substrate or host cell surface. These adhesin complexes are translocated reward by the underlying actin-myosin cytoskeleton, thus propelling the parasite forward. The final step in the conveyor belt is the release of the adhesin at the posterior end of the cell, which occurs by intramembranous proteolysis mediated by a rhomboid-type protease.36 While this model seems inherently inefficient, it provides for several crucial features: (1) adhesins are sheltered from immune recognition until needed for motility (2) apical discharge of adhesins assures directional attachment to the host cell, (3) and rearward translocation of adhesins coupled to cell surface receptors provides for a directional process that drives cell penetration.

Host Cell Recognition and Entry

Despite the fact that T. gondii is capable of invading nearly all types of nucleated cells form its vertebrate hosts, very little is known about specific host cell receptors that are utilized. Time-lapse video microscopy studies indicate that lateral binding and reorientation are not obligatory steps during entry of T. gondii.15,25 Rather invasion occurs when motile parasites contact the host cell with their apical end and this often occurs as a direct consequence of active gliding motility. The process is remarkably rapid and following initial contact entry is complete within 20-30 sec.15 Invasion occurs considerably faster than phagocytosis and is therefore capable of outmaneuvering a phagocytic cell attempting to engulf the parasite.

During host cell invasion, T. gondii attaches to the host cell with the extreme apical end of the parasite (Figs. 1, 2). Invasion is accompanied by sequential discharged three sets of secretory organelles: micronemes, rhoptries, and dense granules.37 Micronemes are discharged first, on cell contact and they contain a family of proteins with adhesive domains including EGF, thrombospondin type I repeats, lectin-like, and integrin A/I domains.34 Most MIC adhesive proteins are only transiently associated with the cell surface before being translocated reward and shed. However, the microneme protein AMA-1 appears to be constitutively present on the parasite apical surface. AMA-1 plays an important role in mediating close apical attachment as invasion is severely impaired at this stage when AMA-1 expression is suppressed.38 A variety of MIC proteins have been shown to participate in cell attachment, although the host cell receptors recognized by these adhesins are less well defined. Interactions with glycosaminoglycans have been implicated in cell attachment.39,40 These interactions are generally low affinity, but multivalent, and thus they facilitate repeated rounds of attachment and release that would be expected to support gliding motility.

Figure 1. Invasion and intracellular niche of Toxoplasma gondii.

Figure 1

Invasion and intracellular niche of Toxoplasma gondii. A) Apical attachment of T. gondii establishes a tight junction between the host cell and parasite membranes. Micronemes (small oval secretory organelles) are clustered at the anterior end of the parasite (more...)

Figure 2. Model depicting the intracellular fate of intracellular T.

Figure 2

Model depicting the intracellular fate of intracellular T. gondii, which occupies a nonfusigenic parasitophorous vacuole (left side). Invasion is accompanied by three successive waves of protein secretion from: (1) micronemes (adhesion), (2) rhoptries (more...)

During parasite invasion, the plasma membrane is stretched to form the parasitophorous vacuole (PV). The integrity of the membrane remains largely intact, and measurements of capacitance across the host cell membrane reveals that the majority of the membrane constituents come from invagination.41 This model is also supported by studies monitoring the redistribution of fluorescently labeled lipids incorporated into the host cell plasma.11,42 Most host cell surface proteins are excluded during entry, as they are apparently unable to pass through the tight junction that forms between the parasite and host cell plasma membranes.11,43 Exclusion of host cell surface proteins likely prevents activation of the endocytic fusion machinery as the newly formed PV lacks cytoplasmic domains from transmemebrane receptors that would otherwise recruit fusion machinery. Consistent with this, the PV membrane remains devoid of markers for endosomes (e.g., transferrin receptor, proton pump, LAMP1 ), or machinery involved in trafficking of endosome and lysosomes (e.g., rabs, NSF ), or antigen presentation (e.g., MHC class I and class II)11 (Fig. 2). Exclusion is evidently important for intracellular survival, as when parasites are opsonized with specific antibodies and engulfed by macrophages they enter into FcR-positive compartment that rapidly acquire markers in the endocytic fusion pathway.11

The mechanism of protein sorting during invasion has remained elusive. Initial models suggested that the large extracellular domains of cell surface proteins physically excluded them from entering the vacuole. However, a number of GPI-anchored proteins were found to readily enter the vacuole during invasion and this process was largely independent of their size.43 Comparison of cell surface ICAM-1 that was tethered in the plasma membrane by a conventional transmembrane domain versus a GPI anchor revealed that exclusion might be related to the partitioning of proteins within the membrane. However, further analysis of this model revealed a more complex sorting process that does not strictly depend on lipid partitioning within the membrane.42 Both raft and nonraft lipids and cytosolic leaflet proteins have access to the vacuole.42 Moreover, single transmembrane proteins may be excluded from the vacuole even when they are preferentially found in rafts.42 Collectively, these studies indicate that multiple mechanisms likely operate to exclude access to the vacuole including membrane fluidity, association with the cytoskeleton, and assembly into oligomeric complexes. Regardless of how this novel process is achieved, it is likely essential for intracellular survival as it assures the absence of signaling molecules that might otherwise drive endocytic fusion with the PV.

Vacuole Modification and Intracellular Survival

The second round of parasite protein secretion that occurs during invasion is associated with discharge of the rhoptries (Fig. 1). These club-shaped organelles form a duct-like structure that connects to the apical end of the parasite. Rhoptries contain a family of proteins (ROPs) that is nonoverlapping with those founding micronemes or dense granules.44 Among the proteins found in the rhoptries are a subset that localize to the neck region of the rhoptry organelle, so called RONs. Recent studies reveal that RONs are localized specifically to the moving junction, a tight constriction that forms between the host and parasite membranes during invasion.45,46 RONs are thus candidates for controlling access of host cell surface components to the vacuole via a process of molecular sieving.

Rhoptry discharge occurs rapidly at the time of entry37 and protein components are released not only into the forming PV but directly into the host cytoplasm47 (Figs. 1, 2). The discharge of rhoptries into the host cell can be accentuated by treating cells with cytochalasin, which blocks entry but not apical attachment.47 Following discharge into the cytosol, ROP proteins acquire a membranous appearance, perhaps by recruiting host membranes, or alternatively perhaps reflecting a contribution of secreted lipids that form membranes de novo. These ROP-rich vesicles as known as “evacuoles” due to their empty profile (Figs. 1, 2). Evacuoles behavior similarly to intact PV in that they avoid fusion with endosomes, recruit mitochondria and ER and traffic within the cell to occupy a paranuclear region.47 The similar properties of evacuoles and the mature PV suggest that ROP proteins mediate many of the key features of the PV. The recent identification of a family of ROP proteins44 may uncover specific functions for parasite proteins that act as effectors with within the host cell. A number of ROP family members contain degenerate kinase domains (unpublished), suggesting they may act to disrupt signaling networks within the host cell. Probable targets for intervention would be host signaling networks, gene transcription, and cytoskeletal turnover.

Discharge of ROP proteins within the PV may also be a mechanism for insertion into the membrane, thus modifying its composition at the time of formation. ROP2 is one such protein that is targeted to the PV where it adopts a transmembrane orientation with the N terminus protruding into the cytosol of the host cell.48 ROP2 undergoes N-terminal processing to expose a sequence resembling a mitochondrial import peptide.49 Insertion of this sequence into the mitochondrial transporter appears to tether the host cell mitochondria to the vacuole.49 This finding explains the long appreciated phenomenon that the PV is tightly wrapped with host cell mitochondria, although it does reveal why this association is important. The prevailing model is that host cell lipids may be acquired from closely opposed ER and mitochondria, and studies using a variety of lipid tracers have revealed uptake pathways that support this model.50

The final chapter in modification of the PV occurs with discharge of dense granules.37 While these organelles are capable of constitutive secretion, kinetic analysis of secretion following invasion reveals that discharge is greatly upregulated within the first 30 min after invasion. Dense granule proteins (referred to as GRA) contain a family of proteins that have little conservation to known proteins. GRA proteins occupy the lumen of the vacuole (GRA1) or are inserted into the PV membrane (GRAs 3 and 5) or are targeted to a membranous network that forms within the vacuole (GRAS 2,4,6).51 The specific functions of these modifications are poorly understood, but these adaptations may contribute to nutrient uptake.

Enclosed with the PV, T. gondii remains sequestered from the host endocytic pathway and the extracellular environment (Figs. 1, 2). While this has obvious advantages in terms of avoiding immune detection, it also presents a challenge for nutrient acquisition. T. gondii may have solved this problem by insertion of protein complexes into the PV to render it porous to small molecules.52 These pores are predicted to allow passage of small metabolites such as amino acids, sugars, cofactors, nucleobases, etc., While the protein composition of these pores has not been defined, it seems likely that they are formed by insertion of either GRA or ROP proteins secreted into the PV. Consistent with this porous vacuole, the genome sequence of T. gondii reveals a large number of transporters that would be predicted to participate in uptake of small molecules from within PV lumen (http:///toxodb.org).

Sequestered within the nonfusigenic vacuole, T. gondii is protected from access to both endogenous and exogenous antigen presentation pathways. Thus, it is thus somewhat surprising that both robust Class I and Class II MHC antigen presentation pathways are elicited during infection.53,54 One explanation for this would be the fact that not all parasites are able to enter cells successfully or avoid lysosomal fusion.8,9 Even a low level of parasite death and digestion might suffice to prime both pathways for presentation. A more intriguing possibility is that select antigens gain access to the cytosol to induce presentation by the class I pathway. The demonstration that many components of rhoptries are injected into the cell during invasion47 provides one possible route for this. A second mechanism has been suggested by recent studies demonstrating that model antigens (Ova) expressed in transgenic parasites can escape from the PV.55 Future studies aimed at identifying the major epitopes recognized during infection may help resolve the pathways by which these antigen reach the respective antigen processing pathways.

Concluding Remarks

There are a number of remaining mysteries about the intracellular survival of T. gondii that have thus far remained elusive. Principle among these is the question of how antigens get processed in both the endogenous and exogenous antigen presentation pathways. Robust class I and class II-mediated responses occur during infection, yet the parasite antigens processed via these pathways remain largely undefined. Equally perplexing is the process by which parasite restricts access of host proteins within the PV during entry. It is unclear if this process occurs by coalescence of lipid rafts or by some other novel form of membrane partitioning. This ability is paramount to the success of T. gondii in entering host cells by creating a novel nonfusigenic compartment. On a broader scale, the ability of T. gondii to infect mononuclear phagocytes may be an important adaptation for dissemination to tissues within the body. Defining to what extent these cells are activated to migrate or to alter their maturation and signaling pathways may provide insight into basic cellular processes in macrophages and the pathogenesis of parasitic infections.

Acknowledgements

I am grateful to members of my laboratory for many helpful discussions and for their contributions to the work cited here and to many colleagues who have provided critical advice and reagents. Supported by the National Institutes of Health.

References

1.
Levine ND. The Protozoan Phylum Apicomplexa. Vols. 1,2. Boca Raton: CRC Press. 1988
2.
Morrissette NS, Sibley LD. Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev. 2002;66:21–38. [PMC free article: PMC120781] [PubMed: 11875126]
3.
Baldauf SL, Roger AJ, Wenk-Siefert I. et al. A kingdom-level phylogeny of eukaryotes based on combined protein data. Science. 2000;290:972–977. [PubMed: 11062127]
4.
Roos DS, Donald RGK, Morrissette NS. et al. Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii. Methods Cell Biol. 1994;45:28–61. [PubMed: 7707991]
5.
Dubey JP, Beattie CP. Toxoplasmosis of animals and man. Boca Raton: CRC Press. 1988
6.
Channon JY, Seguin RM, Kasper LH. Differential infectivity and division of Toxoplasma gondii in human peripheral blood leukocytes. Infect Immun. 2000;68:4822–4826. [PMC free article: PMC98447] [PubMed: 10899898]
7.
Wilson CB, Tsai V, Remington JS. Failure to trigger the oxidative burst of normal macrophages. J Exp Med. 1980;151:328–346. [PMC free article: PMC2185778] [PubMed: 7356726]
8.
Jones TC, Hirsch JG. The interaction of Toxoplasma gondii and mammalian cells. II The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J Exp Med. 1972;136:1173–1194. [PMC free article: PMC2139290] [PubMed: 4343243]
9.
Jones TC, Yeh S, Hirsch JG. The interaction between Toxoplasma gondii and mammalian cells. I. Mechanism of entry and intracellular fate of the parasite. J Exp Med. 1972;136:1157–1172. [PMC free article: PMC2139313] [PubMed: 5082671]
10.
Sibley LD, Weidner E, Krahenbuhl JL. Phagosome acidification blocked by intracellular Toxoplasma gondii. Nature. 1985;315:416–419. [PubMed: 2860567]
11.
Mordue DG, Sibley LD. Intracellular fate of vacuoles containing Toxoplasma gondii is determined at the time of formation and depends on the mechanism of entry. J Immunol. 1997;159:4452–4459. [PubMed: 9379044]
12.
Petersen E, Dubey JP. Biology of toxoplasmosis. In: Joynson DH, Wreghitt TJ, eds. Toxoplasmosis: A comprehensive Clinical Guide. Cambridge: University Press. 2001:1–42.
13.
King CA. Cell motility of sporozoan protozoa. Parasitol Today. 1988;11:315–318. [PubMed: 15463014]
14.
Sibley LD. Invasion strategies of intracellular parasites. Science. 2004;304:248–253. [PubMed: 15073368]
15.
Håkansson S, Morisaki H, Heuser JE. et al. Time-lapse video microscopy of gliding motility in Toxoplasma gondii reveals a novel, biphasic mechanism of cell locomotion. Mol Biol Cell. 1999;10:3539–3547. [PMC free article: PMC25631] [PubMed: 10564254]
16.
Barragan A, Sibley LD. Transepithelial migration of Toxoplasma gondii is linked to parasite motility and virulence. J Exp Med. 2002;195:1625–1633. [PMC free article: PMC2193562] [PubMed: 12070289]
17.
Barragan A, Sibley LD. Migration of Toxoplasma gondii across biological barriers. Trends Microbiol. 2003;11:426–430. [PubMed: 13678858]
18.
Arrowood MJ, Sterling CR, Healey MC. Immunofluorescent microscopical visualization of trails left by gliding Cryptosporidium parvum sporozoites. J Parasitol. 1991;77:315–317. [PubMed: 2010865]
19.
King CA. Cell surface interaction of the protozoan Gregarina with Concanavalin A beads - Implications for models of gregarine gliding. Cell Biol Intl Rep. 1981;5:297–305. [PubMed: 6783325]
20.
Clark DP, Sears CL. The pathogenesis of cryptosporidiosis. Parasitol Today. 1996;12:221–225. [PubMed: 15275201]
21.
Wetzel DM, Schmidt J, Kuhlenschmidt M. et al. Gliding motility leads to active cellular invasion by Cryptosporidium parvum sporozoites. Infect Immun. 2005;73:5379–5387. [PMC free article: PMC1231075] [PubMed: 16113253]
22.
Ryning FW, Remington JS. Effect of cytochalasin D on Toxoplasma gondii cell entry. Infect Immun. 1978;20:739–743. [PMC free article: PMC421921] [PubMed: 669821]
23.
Miller LH, Aikawa M, Johnson JG. et al. Interaction between cytochalasin B-treated malarial parasites and erythrocytes. J Exp Med. 1979;149:172–184. [PMC free article: PMC2184746] [PubMed: 105074]
24.
Dobrowolski JM, Sibley LD. Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. Cell. 1996;84:933–939. [PubMed: 8601316]
25.
Morisaki JH, Heuser JE, Sibley LD. Invasion of Toxoplasma gondii occurs by active penetration of the host cell. J Cell Sci. 1995;108:2457–2464. [PubMed: 7673360]
26.
Wetzel DM, Håkansson S, Hu K. et al. Actin filament polymerization regulates gliding motility by apicomplexan parasites. Mol Biol Cell. 2003;14:396–406. [PMC free article: PMC149980] [PubMed: 12589042]
27.
Gaskins E, Gilk S, DeVore N. et al. Identification of the membrane receptor of a class XIV myosin Toxoplasma gondii. J Cell Biol. 2004;165:383–393. [PMC free article: PMC2172186] [PubMed: 15123738]
28.
Meissner M, Schluter D, Soldati D. Role of Toxoplasma gondii myosin A in powering parasite gliding and host cell invasion. Science. 2002;298:837–840. [PubMed: 12399593]
29.
Ménard R. Gliding motility and cell invasion by Apicomplexa: Insights from the Plasmodium sporozoite. Cell Micro. 2001;3:63–73. [PubMed: 11207621]
30.
Jewett TJ, Sibley LD. Aldolase forms a bridge between cell surface adhesins and the actin cytoskeleton in apicomplexan parasites. Molec Cell. 2003;11:885–894. [PubMed: 12718875]
31.
Buscaglia CA, Coppens I, Hol WGJ. et al. Site of interaction between aldolase and thrombospondinrelated anonymous protein in Plasmodium. Mol Biol Cell. 2003;14:4947–4957. [PMC free article: PMC284797] [PubMed: 14595113]
32.
Kappe S, Bruderer T, Gantt S. et al. Conservation of a gliding motility and cell invasion machinery in apicomplexan parasites. J Cell Biol. 1999;147:937–943. [PMC free article: PMC2169348] [PubMed: 10579715]
33.
Jewett TJ, Sibley LD. The Toxoplasma proteins MIC2 and M2AP for a hexameric complex necessary for intracellular survival. J Biol Chem. 2004;275:9362–9369. [PubMed: 14670959]
34.
Soldati D, Dubremetz JF, Lebrun M. Microneme proteins: Structural and functional requirements to promote adhesion and invasion by the apicomplexan parasite Toxoplasma gondii. Int J Parasitol. 2001;31:1293–1302. [PubMed: 11566297]
35.
Carruthers VB, Giddings OK, Sibley LD. Secretion of micronemal proteins is associated with Toxoplasma invasion of host cells. Cell Microbiol. 1999;1:225–236. [PubMed: 11207555]
36.
Brossier F, Jewett TJ, Sibley LD. et al. A spatially-localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. Proc Natl Acad Sci USA. 2005;102:4146–4151. [PMC free article: PMC554800] [PubMed: 15753289]
37.
Carruthers VB, Sibley LD. Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol. 1997;73:114–123. [PubMed: 9208224]
38.
Mital J, Meissner M, Soldati D. et al. Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell invasion. Mol Biol Cell. 2005;16:4341–4349. [PMC free article: PMC1196342] [PubMed: 16000372]
39.
Carruthers VB, Håkansson S, Giddings OK. et al. Toxoplasma gondii uses sulfated proteoglycans for substrate and host cell attachment. Infect Immun. 2000;68:4005–4011. [PMC free article: PMC101681] [PubMed: 10858215]
40.
Ortega-Barria E, Boothroyd JC. A Toxoplasma lectin-like activity specific for sulfated polysaccharides is involved in host cell infection. J Biol Chem. 1999;274:1267–1276. [PubMed: 9880495]
41.
Suss-Toby E, Zimmerberg J, Ward GE. Toxoplasma invasion: The parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fusion pore. Proc Natl Acad Sci USA. 1996;93:8413–8418. [PMC free article: PMC38685] [PubMed: 8710885]
42.
Charron AJ, Sibley LD. Molecular partitioning during host cell penetration by Toxoplasma gondii. Taffic. 2004;5:855–867. [PubMed: 15479451]
43.
Mordue DG, Desai N, Dustin M. et al. Invasion by Toxoplasma gondii establishes a moving junction that selectively excludes host cell plasma membrane proteins on the basis of their membrane anchoring. J Exp Med. 1999;190:1783–1792. [PMC free article: PMC2195726] [PubMed: 10601353]
44.
Bradley PJ, Ward C, Cheng SJ. et al. Proteomic analysis of rhoptry organelles reveals many novel constituents for host-parasite interactions in T. gondii. J Biol Chem. 2005;280:34245–34258. [PubMed: 16002398]
45.
Alexander DL, Mital J, Ward GE. et al. Identification of the moving junction complex of Toxoplasma gondii: A collaboration between distinct secretory organelles. PLos Path. 2005;1:137–149. [PMC free article: PMC1262624] [PubMed: 16244709]
46.
Lebrun M, Michelin A, El Hajj H. et al. The rhoptry neck protein RON4 relocalizes at the moving junction during Toxoplasma gondii invasion. Cell Micro. 2005;7:1823–1833. [PubMed: 16309467]
47.
Håkansson S, Charron AJ, Sibley LD. Toxoplasma evacuoles: A two-step process of secretion and fusion forms the parasitophorous vacuole. EMBO J. 2001;20:3132–3144. [PMC free article: PMC150190] [PubMed: 11406590]
48.
Beckers CJM, Dubremetz JF, Mercereau-Puijalon O. et al. The Toxoplasma gondii rhoptry protein ROP2 is inserted into the parasitophorous vacuole membrane, surrounding the intracellular parasite, and is exposed to the host cell cytoplasm. J Cell Biol. 1994;127:947–961. [PMC free article: PMC2200062] [PubMed: 7962077]
49.
Sinai AP, Joiner KA. The Toxoplasma gondii protein ROP2 mediates host organelle association with the parasitophorous vacuole membrane. J Cell Biol. 2001;154:95–108. [PMC free article: PMC2196872] [PubMed: 11448993]
50.
Charron AJ, Sibley LD. Host cells: Mobilizable lipid resources for the intracellular parasite Toxoplasma gondii. J Cell Sci. 2002;115:3049–3059. [PubMed: 12118061]
51.
Mercier C, Dubremetz JF, Rauscher B. et al. Biogenesis of nanotubular network in Toxoplasma parasitophorous vacuole induced by parasite proteins. Mol Biol Cell. 2002;13:2397–2409. [PMC free article: PMC117322] [PubMed: 12134078]
52.
Schwab JC, Beckers CJM, Joiner KA. The parasitophorous vacuole membrane surrounding intracellular Toxoplasma gondii functions as a molecular sieve. Proc Natl Acad Sci USA. 1994;91:509–513. [PMC free article: PMC42978] [PubMed: 8290555]
53.
Hunter CA, Reichmann G. Immunology of toxoplasma infection. In: Joynson DH, Wreghitt TJ, eds. Toxoplasmosis: A Comprehensive Clinical Guide. Cambridge University Press. 2001:43–57.
54.
Denkers EY, Gazzinelli RT. Regulation and function of T-cell mediated immunity during Toxoplasma gondii infection. Clin Micro Rev. 1998;11:569–588. [PMC free article: PMC88897] [PubMed: 9767056]
55.
Gubbels MJ, Streipen B, Shastri N. et al. Class I major histocompatibility complex presentation of antigens that escape from the parasitophorous vacuole of Toxoplasma gondii. Infect Immun. 2005;73:703–711. [PMC free article: PMC547086] [PubMed: 15664908]
56.
Sibley LD. Toxoplasma gondii: Perfecting an intracellular life style. Traffic. 2003;4:581–586. [PubMed: 12911812]
Copyright © 2000-2013, Landes Bioscience.
Bookshelf ID: NBK6450

Views

  • PubReader
  • Print View
  • Cite this Page

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...