Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi

Maeda, Fernando Yukio; Cortéz, Cristian; Alves, Renan Melatto; Yoshida, Nobuko

doi:10.1016/j.actatropica.2011.10.017

Cited by 29 publications

(39 citation statements)

References 31 publications

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“…In T. cruzi , pathogen-associated molecular patterns involve a great number of surface molecules that induce changes in cell signaling of host cells [1]. The early cell infection by cell-derived trypomastigotes involves adhesion, penetration, and transit through host cell parasitophorous vacuoles in order to establish an intracellular infection.…”

Section: Introductionmentioning

confidence: 99%

EarlyTrypanosoma cruziInfection Reprograms Human Epithelial Cells

Chiribao

Libisch

Parodi-Talice

et al. 2014

BioMed Research International

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Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response), a great number of transcription factors (including the majority of NFκB family members), and host metabolism (cholesterol, fatty acids, and phospholipids). These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination.

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Section: Introductionmentioning

confidence: 99%

EarlyTrypanosoma cruziInfection Reprograms Human Epithelial Cells

Chiribao

Libisch

Parodi-Talice

et al. 2014

BioMed Research International

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“…Bats infected by T. cruzi -like species show nests of amastigotes in cardiac, skeletal and stomach muscle cells likewise T. cruzi in a range of hosts including man. Recent studies demonstrated that T. dionisii and T. cruzi invade mammalian cells through a common mechanism involving lysosome mobilization to the site of parasite entry [15], [16]. Previous studies showed that T. cruzi and T. dionisii share similar molecules with important roles in host-parasite interactions such as phospholipids and cysteine proteases [17], [18] as well as epitopes associated to autoimmunity in Chagas disease [19].…”

Section: Introductionmentioning

confidence: 99%

Repertoire, Genealogy and Genomic Organization of Cruzipain and Homologous Genes in Trypanosoma cruzi, T. cruzi-Like and Other Trypanosome Species

et al. 2012

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Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

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“…PTK phosphorylates p175, a protein undetectable in noninvasive epimastigote forms . Distinct from the parasite response, host cell PTK is not implicated in gp82-dependent MT invasion, rather signaling pathways involving lipid kinase PI3K, mammalian target of rapamycin (mTOR), PKC and PLC may be activated and Ca 2+ appears to be released from IP 3 -sensitive compartments or in IP 3 -independent manner (Ferreira et al 2006 ;Martins et al 2011 ;Maeda et al 2012 , Fig. 6.4 ).…”

Section: Gastric Mucin-binding Property Of Gp82 and Mt Migrationmentioning

confidence: 93%

“…6.4 ). In addition to protein kinase C (PKC), which may be activated by DAG, phosphatidylinositol 3-kinase (PI3K) and protein tyrosine kinase (PTK) also participate in MT invasion process (Maeda et al 2012 ). PTK phosphorylates p175, a protein undetectable in noninvasive epimastigote forms .…”

Section: Gastric Mucin-binding Property Of Gp82 and Mt Migrationmentioning

confidence: 99%

The gp82 Surface Molecule of Trypanosoma cruzi Metacyclic Forms

Cortéz

Sobreira

Maeda

et al. 2013

Subcellular Biochemistry

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Gp82 is a surface glycoprotein expressed in Trypanosoma cruzi metacyclic trypomastigotes, the parasite forms from the insect vector that initiate infection in the mammalian host. Studies with metacyclic forms generated in vitro, as counterparts of insect-borne parasites, have shown that gp82 plays an essential role in host cell invasion and in the establishment of infection by the oral route. Among the gp82 properties relevant for infection are the gastric mucin-binding capacity and the ability to induce the target cell signaling cascades that result in actin cytoskeleton disruption and lysosome exocytosis, events that facilitate parasite internalization. The gp82 sequences from genetically divergent T. cruzi strains are highly conserved, displaying >90 % identity. Both the host cell-binding sites, as well as the gastric mucin-binding sequence of gp82, are localized in the C-terminal domain of the molecule. In the gp82 structure model, the main cell-binding site consists of an α-helix, which connects the N-terminal β-propeller domain to the C-terminal β-sandwich domain, where the second cell binding site is nested. The two cell binding sites are fully exposed on gp82 surface. Downstream and close to the α-helix is the gp82 gastric mucin-binding site, which is partially exposed. All available data support the notion that gp82 is structurally suited for metacyclic trypomastigote invasion of host cells and for initiating infection by the oral route.

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Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi

Cited by 29 publications

References 31 publications

EarlyTrypanosoma cruziInfection Reprograms Human Epithelial Cells

EarlyTrypanosoma cruziInfection Reprograms Human Epithelial Cells

Repertoire, Genealogy and Genomic Organization of Cruzipain and Homologous Genes in Trypanosoma cruzi, T. cruzi-Like and Other Trypanosome Species

The gp82 Surface Molecule of Trypanosoma cruzi Metacyclic Forms

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