Parasite-host glycan interactions during Trypanosoma cruzi infection: trans-Sialidase rides the show

Campetella, Oscar; Buscaglia, Carlos A.; Mucci, Juan; Leguizamón, María Susana

doi:10.1016/j.bbadis.2020.165692

Cited by 33 publications

(57 citation statements)

References 117 publications

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“…TS and iTS Both PI3K/Akt and MAPK/Erk Promotion of invasion and sialylation pattern Butler et al, 2013;Campetella et al, 2020) Tc85 Surface ERK1/2 Host cell attachment and invasion (Magdesian et al, 2007;Mattos et al, 2014) TSSA Surface ERK1/2 Host cell attachment and Ca 2+ signaling (Cańepa et al, 2012a;Caḿara et al, 2017) TcOPB Secreted PLC and Rac1 Produces an unknown structure soluble factor that triggers Ca 2+ mobilization (Caler et al, 1998;Motta et al, 2019) Extracellular (Wainszelbaum et al, 2001;Belaunzarań et al, 2007) All forms Cruzipain Secreted PI3K/Akt and MEK/ERK Ca 2+ signaling (Taketo et al, 1997;San Francisco et al, 2017) gp90 was observed in a poor invasive strain (G) (Ruiz et al, 1998). Although gp90 binds to the host cell, it fails to trigger cytosolic Ca 2+ mobilization (Ruiz et al, 1998).…”

Section: -Gp90mentioning

confidence: 99%

“…Among the different surface molecules involved in TCTs invasion is the unique T. cruzi trans-sialidase (TS), an important parasite virulence factor. Unable to synthesize sialic acid (SA), TS enables TCTs to transfer terminal SA residues linked a2,3 to terminal b-galactopyranoses from host cell donor macromolecules to glycans of mucin-type proteins displayed on the parasite membrane (Schenkman et al, 1991;da Fonseca et al, 2019;Campetella et al, 2020). The generation of a sialylated surface plays a central role in promoting the evasion of immune responses, favoring survival and the establishment of the chronic disease (Nardy et al, 2016).…”

Section: Cell-derived Trypomastigotes -Trans-sialidasementioning

confidence: 99%

See 1 more Smart Citation

All Roads Lead to Cytosol: Trypanosoma cruzi Multi-Strategic Approach to Invasion

Ferri

Edreira

2021

Front. Cell. Infect. Microbiol.

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T. cruzi has a complex life cycle involving four developmental stages namely, epimastigotes, metacyclic trypomastigotes, amastigotes and bloodstream trypomastigotes. Although trypomastigotes are the infective forms, extracellular amastigotes have also shown the ability to invade host cells. Both stages can invade a broad spectrum of host tissues, in fact, almost any nucleated cell can be the target of infection. To add complexity, the parasite presents high genetic variability with differential characteristics such as infectivity. In this review, we address the several strategies T. cruzi has developed to subvert the host cell signaling machinery in order to gain access to the host cell cytoplasm. Special attention is made to the numerous parasite/host protein interactions and to the set of signaling cascades activated during the formation of a parasite-containing vesicle, the parasitophorous vacuole, from which the parasite escapes to the cytosol, where differentiation and replication take place.

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Section: -Gp90mentioning

confidence: 99%

Section: Cell-derived Trypomastigotes -Trans-sialidasementioning

confidence: 99%

All Roads Lead to Cytosol: Trypanosoma cruzi Multi-Strategic Approach to Invasion

Ferri

Edreira

2021

Front. Cell. Infect. Microbiol.

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“…Lastly, some studies showed that thymic atrophy was not induced by a non-virulent strain of T. cruzi , suggesting that parasite-derived virulence factors may be involved in the death of thymocytes. In keeping with this hypothesis, some studies indicate that the parasite-derived enzyme trans-sialidase may be involved in the thymic atrophy ( 83 , 84 ). Despite that T. cruzi can infect the thymus ( 43 , 46 , 58 ) and release locally antigens, some studies have shown that when trans-sialidase is artificially shed to circulation, it induces thymocyte apoptosis ( 85 ).…”

Section: Thymocyte Depletion In Acute Trypanosoma Cruzi mentioning

confidence: 87%

The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

et al. 2020

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Chagas disease, caused by the protozoan parasite T. cruzi , is a prevalent parasitic disease in Latin America. Presently, it is spreading around the world by human migration, thus representing a new global health issue. Chronically infected individuals reveal a dissimilar disease progression: while nearly 60% remain without apparent disease for life, 30% develop life-threatening pathologies, such as chronic chagasic cardiomyopathy (CCC) or megaviscerae. Inflammation driven by parasite persistence seems to be involved in the pathophysiology of the disease. However, there is also evidence of the occurrence of autoimmune events, mainly caused by molecular mimicry and bystander activation. In experimental models of disease, is well-established that T. cruzi infects the thymus and causes locally profound structural and functional alterations. The hallmark is a massive loss of CD4 + CD8 + double positive (DP) thymocytes, mainly triggered by increased levels of glucocorticoids, although other mechanisms seem to act simultaneously. Thymic epithelial cells (TEC) exhibited an increase in extracellular matrix deposition, which are related to thymocyte migratory alterations. Moreover, medullary TEC showed a decreased expression of AIRE and altered expression of microRNAs, which might be linked to a disrupted negative selection of the T-cell repertoire. Also, almost all stages of thymocyte development are altered, including an abnormal output of CD4 − CD8 − double negative (DN) and DP immature and mature cells, many of them carrying prohibited TCR-Vβ segments. Evidence has shown that DN and DP cells with an activated phenotype can be tracked in the blood of humans with chronic Chagas disease and also in the secondary lymphoid organs and heart of infected mice, raising new questions about the relevance of these populations in the pathogenesis of Chagas disease and their possible link with thymic alterations and an immunoendocrine imbalance. Here, we discuss diverse molecular mechanisms underlying thymic abnormalities occurring during T. cruzi infection and their link with CCC, which may contribute to the design of innovative strategies to control Chagas disease pathology.

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“…The negatively charged glycans protect the parasite from the action of proteases and other enzymes [ 32 , 34 , 36 , 37 ]. This is the only way for T. cruzi to acquire the sialic acid needed for infection [ 15 , 38 ]. The reaction depends on the structure of the O -linked sugars in the mucins; more precisely, on the presence of β-Gal p terminal units ( Figure 3 ).…”

Section: The Glycan In Mucins Of T Cruzimentioning

confidence: 99%

“…Higher oligosaccharides were released from the mucins via a reductive β-elimination reaction [ 98 ]. Although the structure of the branched oligosaccharides was not fully described, the methylation studies pointed to branching at C-6 of the GlcNAc with Gal p , which should be in the β-configuration so as to function as an acceptor in the transfer reaction of sialic acid from host glycoconjugates [ 33 , 34 , 38 ]. This process is crucial for the pathogenesis of T. cruzi , since the lysis of trypomastigotes is prevented by sialylation [ 30 , 99 ].…”

Section: Structure Of Glycans In Mucins From Mammalian Cell-derivementioning

confidence: 99%

The Glycan Structure of T. cruzi mucins Depends on the Host. Insights on the Chameleonic Galactose

Giorgi

Lederkremer

2020

Molecules

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Trypanosoma cruzi, the protozoa that causes Chagas disease in humans, is transmitted by insects from the Reduviidae family. The parasite has developed the ability to change the structure of the surface molecules, depending on the host. Among them, the mucins are the most abundant glycoproteins. Structural studies have focused on the epimastigotes and metacyclic trypomastigotes that colonize the insect, and on the mammal trypomastigotes. The carbohydrate in the mucins fulfills crucial functions, the most important of which being the accepting of sialic acid from the host, a process catalyzed by the unique parasite trans-sialidase. The sialylation of the parasite influences the immune response on infection. The O-linked sugars have characteristics that differentiate them from human mucins. One of them is the linkage to the polypeptide chain by the hexosamine, GlcNAc, instead of GalNAc. The main monosaccharide in the mucins oligosaccharides is galactose, and this may be present in three configurations. Whereas β-d-galactopyranose (β-Galp) was found in the insect and the human stages of Trypanosoma cruzi, β-d-galactofuranose (β-Galf) is present only in the mucins of some strains of epimastigotes and α-d-galactopyranose (α-Galp) characterizes the mucins of the bloodstream trypomastigotes. The two last configurations confer high antigenic properties. In this review we discuss the different structures found and we pose the questions that still need investigation on the exchange of the configurations of galactose.

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Parasite-host glycan interactions during Trypanosoma cruzi infection: trans-Sialidase rides the show

Cited by 33 publications

References 117 publications

All Roads Lead to Cytosol: Trypanosoma cruzi Multi-Strategic Approach to Invasion

All Roads Lead to Cytosol: Trypanosoma cruzi Multi-Strategic Approach to Invasion

The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

The Glycan Structure of T. cruzi mucins Depends on the Host. Insights on the Chameleonic Galactose

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