Host cell surface sialic acid residues are involved on the process of penetration of<i>Toxoplasma gondii</i>into mammalian cells

Monteiro, V.G; Soares, Cleiton de Paula; Souza, Wanderley de

doi:10.1111/j.1574-6968.1998.tb13105.x

Cited by 57 publications

(17 citation statements)

References 14 publications

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“…Some bacterial pathogens exploit this interaction by either scavenging sialic acid to coat their surfaces or synthesizing their own to recruit FH and thereby protect their surface from complement attack (64)(65)(66). Several studies have demonstrated that T. gondii possess a lectin like activity associated with its ability to interact with host SPGs (67,68) and sialic acid (69,70). It has been reported that C4BP also contains a binding domain for heparin (63).…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Recruits Factor H and C4b-Binding Protein to Mediate Resistance to Serum Killing and Promote Parasite Persistence in vivo

2020

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Regulating complement is an important step in the establishment of infection by microbial pathogens. Toxoplasma gondii actively resists complement-mediated killing in non-immune human serum (NHS) by inactivating C3b, however the precise molecular basis is unknown. Here, a flow cytometry-based C3b binding assay demonstrated that Type II strains had significantly higher levels of surface-bound C3b than Type I strains. However, both strains efficiently inactivated C3b and were equally resistant to serum killing, suggesting that resistance is not strain-dependent. Toxoplasma activated both the lectin (LP) and alternative (AP) pathways, and the deposition of C3b was both strain and lectin-dependent. A flow cytometry-based lectin binding assay identified strain-specific differences in the level and heterogeneity of surface glycans detected. Specifically, increased lectin-binding by Type II strains correlated with higher levels of the LP recognition receptor mannose binding lectin (MBL). Western blot analyses demonstrated that Toxoplasma recruits both classical pathway (CP) and LP regulator C4b-binding proteins (C4BP) and AP regulator Factor H (FH) to the parasite surface to inactivate bound C3b-iC3b and C3dg and limit formation of the C5b-9 attack complex. Blocking FH and C4BP contributed to increased C5b-9 formation in vitro. However, parasite susceptibility in vitro was only impacted when FH was blocked, indicating that down regulation of the alternative pathway by FH may be more critical for parasite resistance. Infection of C3 deficient mice led to uncontrolled parasite growth, acute mortality, and reduced antibody production, indicating that both the presence of C3, and the ability of the parasite to inactivate C3, was protective. Taken together, our results establish that Toxoplasma regulation of the complement system renders mice resistant to acute infection by limiting parasite proliferation in vivo, but susceptible to chronic infection, with all mice developing transmissible cysts to maintain its life cycle.

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Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Recruits Factor H and C4b-Binding Protein to Mediate Resistance to Serum Killing and Promote Parasite Persistence in vivo

2020

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“…Tachyzoites bind vascular endothelium in intact human retina under flow conditions (Chipps et al, 2006), and the binding-invasion step occurs relatively quickly for human retinal endothelial cells (Zamora et al, 2008). Sulfated proteoglycans have been implicated as host receptors on non-endothelial cells (Carruthers et al, 2000; Monteiro et al, 1998; Ortega-Barria and Boothroyd, 1999). In this respect, results of our gene expression microarray study might be relevant, showing that human retinal endothelial cells express relatively high levels of multiple sulfotransferases.…”

Section: Infectious Posterior Uveitismentioning

confidence: 99%

Role of the retinal vascular endothelial cell in ocular disease

Bharadwaj

Appukuttan

Wilmarth

et al. 2013

Progress in Retinal and Eye Research

136

114

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Retinal endothelial cells line the arborizing microvasculature that supplies and drains the neural retina. The anatomical and physiological characteristics of these endothelial cells are consistent with nutritional requirements and protection of a tissue critical to vision. On the one hand, the endothelium must ensure the supply of oxygen and other nutrients to the metabolically active retina, and allow access to circulating cells that maintain the vasculature or survey the retina for the presence of potential pathogens. On the other hand, the endothelium contributes to the blood-retinal barrier that protects the retina by excluding circulating molecular toxins, microorganisms, and pro-inflammatory leukocytes. Features required to fulfill these functions may also predispose to disease processes, such as retinal vascular leakage and neovascularization, and trafficking of microbes and inflammatory cells. Thus, the retinal endothelial cell is a key participant in retinal ischemic vasculopathies that include diabetic retinopathy and retinopathy of prematurity, and retinal inflammation or infection, as occurs in posterior uveitis. Using gene expression and proteomic profiling, it has been possible to explore the molecular phenotype of the human retinal endothelial cell and contribute to understanding of the pathogenesis of these diseases. In addition to providing support for the involvement of well-characterized endothelial molecules, profiling has the power to identify new players in retinal pathologies. Findings may have implications for the design of new biological therapies. Additional progress in this field is anticipated as other technologies, including epigenetic profiling methods, whole transcriptome shotgun sequencing, and metabolomics, are used to study the human retinal endothelial cell.

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“…There are two known factors in the host cell invasion by T. gondii, including parasite-derived proteins and receptors on the host cell surface. It is known that abundant carbohydrate molecules on host cell surface, such as sialic acid, heparan sulfate and chondroitin sulfate, are receptors for T. gondii invasion (Monteiro et al, 1998;Carruthers et al, 2000;Baba et al, 2015), but the parasite ligands interacting with these receptors have not been well-characterized.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, merozoites of Plasmodium falciparum recognize and interact with N-acetylneuraminic acid residues on red blood cell (RBC) for erythrocyte invasion (Malpede et al, 2013), and Trypanosoma cruzi can invade macrophage by parasite trans-sialidase transfering sialic-acid residues from host glycoconjugates to parasite mucins (Morrot, 2013). It has been reported that the infection rate of T. gondii for the sialic acid-lacking mutant host cells was lower than that for wild type cells (Monteiro et al, 1998). Also, it was observed about 90% reduction of invasion efficiency when N-acetylneuraminic acid (NANA) was used as a competitor or when host cells were treated with neuraminidase (Blumenschein et al, 2007;Friedrich et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The Putative TCP-1 Chaperonin Is an Important Player Involved in Sialic Acid-Dependent Host Cell Invasion by Toxoplasma gondii

et al. 2020

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Host cell invasion by Toxoplasma gondii is crucial for the survival and proliferation of parasite. The process of T. gondii tachyzoite invasion requires interaction between parasite proteins and receptors on the surface of host cells. Sialic acid is one of the important receptors for host cell invasion by T. gondii. However, the parasitederived proteins interacting with sialic acid have not been well characterized. In this study, a novel protein named putative TCP-1 chaperonin (TGME49_318410) in T. gondii (TgTCP-1) was targeted and characterized. TgTCP-1 protein colocalized with MIC3 protein, which could be secreted from T. gondii tachyzoites, and this protein showed a specific binding activity to sialic acid, and DC and Vero cells in vitro. The binding of TgTCP-1 protein to DC and Vero cells were inhibited by either pre-incubation with free sialic acid or neuraminidase treatment of the cells. Moreover, a significant reduction of T. gondii invasion in Vero cells was observed after pre-incubation of the cells with recombinant TgTCP-1 protein. These results illustrated that TgTCP-1 is an important molecule involved in sialic acid-dependent host cell invasion by T. gondii.

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Host cell surface sialic acid residues are involved on the process of penetration ofToxoplasma gondiiinto mammalian cells

Cited by 57 publications

References 14 publications

Toxoplasma gondii Recruits Factor H and C4b-Binding Protein to Mediate Resistance to Serum Killing and Promote Parasite Persistence in vivo

Toxoplasma gondii Recruits Factor H and C4b-Binding Protein to Mediate Resistance to Serum Killing and Promote Parasite Persistence in vivo

Role of the retinal vascular endothelial cell in ocular disease

The Putative TCP-1 Chaperonin Is an Important Player Involved in Sialic Acid-Dependent Host Cell Invasion by Toxoplasma gondii

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