scholarly journals Infectivity of Trypanosoma cruzi strains is associated with differential expression of surface glycoproteins with differential Ca2+ signalling activity

1998 ◽  
Vol 330 (1) ◽  
pp. 505-511 ◽  
Author(s):  
C. Rita RUIZ ◽  
Silvio FAVORETO ◽  
L. Miriam DORTA ◽  
E. M. Maria OSHIRO ◽  
T. Alice FERREIRA ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Hela Cells ◽  
Strain Analysis ◽  
Inverse Correlation ◽  
Host Cells ◽  
Target Cells ◽  
Metacyclic Trypomastigotes ◽  
Cell Components ◽  
Major Surface ◽  
Surface Glycoproteins

Mammalian cell invasion assays, using metacyclic trypomastigotes of Trypanosoma cruzi G and CL strains, showed that the CL strain enters target cells in several-fold higher numbers as compared with the G strain. Analysis of expression of surface glycoproteins in metacyclic forms of the two strains by iodination, immunoprecipitation and FACS, revealed that gp90, undetectable in the CL strain, is one of the major surface molecules in the G strain, that expression of gp82 is comparable in both strains and that gp35/50 is expressed at lower levels in the CL strain. Purified gp90 and gp35/50 bound more efficiently than gp82 to cultured HeLa cells. However, the intensity of the Ca2+ response triggered in HeLa cells by gp82 was significantly higher than that induced by gp35/50 or gp90. Most of the Ca2+ signalling activity of the metacyclic extract towards HeLa cells was due to gp82 and was inhibitable by gp82-specific monoclonal antibody 3F6. Ca2+ mobilization was also triggered in metacyclic trypomastigotes by host-cell components; it was mainly gp82-mediated and more intense in the CL than in the G strain. We propose that expression of gp90 and gp35/50 at high levels impairs binding of metacyclic forms to host cells through productive gp82-mediated interaction, which leads to the target-cell and parasite Ca2+ mobilization required for invasion. Analysis of metacyclic forms of eight additional T. cruzi strains corroborated the inverse correlation between infectivity and expression of gp90 and gp35/50.

scholarly journals Molecular basis of mammalian cell invasion by Trypanosoma cruzi

2006 ◽  
Vol 78 (1) ◽  
pp. 87-111 ◽  
Author(s):  
Nobuko Yoshida
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Invasion ◽  
Target Cell ◽  
Protein Tyrosine Kinase ◽  
Host Cells ◽  
Target Cells ◽  
Cytokeratin 18 ◽  
Parasite Protein ◽  
Oligopeptidase B ◽  
Surface Glycoproteins

Establishment of infection by Trypanosoma cruzi, the agent of Chagas' disease, depends on a series of events involving interactions of diverse parasite molecules with host components. Here we focus on the mechanisms of target cell invasion by metacyclic trypomastigotes (MT) and mammalian tissue culture trypomastigotes (TCT). During MT or TCT internalization, signal transduction pathways are activated both in the parasite and the target cell, leading to Ca2+ mobilization. For cell adhesion, MT engage surface glycoproteins, such as gp82 and gp35/50, which are Ca2+ signal-inducing molecules. In T. cruzi isolates that enter host cells in gp82-mediated manner, parasite protein tyrosine kinase as well as phospholipase C are activated, and Ca2+ is released from I P3-sensitive stores, whereas in T. cruzi isolates that attach to target cells mainly through gp35/50, the signaling pathway involving adenylate cyclase appears to be stimulated, with Ca2+ release from acidocalciosomes. In addition, T. cruzi isolate-dependent inhibitory signals, mediated by MT-specific gp90, may be triggered both in the host cell and the parasite. The repertoire of TCT molecules implicated in cell invasion includes surface glycoproteins of gp85 family, with members containing binding sites for laminin and cytokeratin 18, enzymes such as cruzipain, trans-sialidase, and an oligopeptidase B that generates a Ca2+-agonist from a precursor molecule.

scholarly journals Mammalian cell invasion and intracellular trafficking by Trypanosoma cruzi infective forms

2005 ◽  
Vol 77 (1) ◽  
pp. 77-94 ◽  
Author(s):  
Renato A. Mortara ◽  
Walter K. Andreoli ◽  
Noemi N. Taniwaki ◽  
Adriana B. Fernandes ◽  
Claudio V. da Silva ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Mammalian Cells ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
Mammalian Host ◽  
Target Cells ◽  
Sylvatic Cycle ◽  
Final Destination ◽  
Different Strains

Trypanosoma cruzi, the etiological agent of Chagas’ disease, occurs as different strains or isolates that may be grouped in two major phylogenetic lineages: T. cruzi I, associated with the sylvatic cycle and T. cruzi II, linked to the human disease. In the mammalian host the parasite has to invade cells and many studies implicated the flagellated trypomastigotes in this process. Several parasite surface components and some of host cell receptors with which they interact have been identified. Our work focused on how amastigotes, usually found growing in the cytoplasm, can invade mammalian cells with infectivities comparable to that of trypomastigotes. We found differences in cellular responses induced by amastigotes and trypomastigotes regarding cytoskeletal components and actin-rich projections. Extracellularly generated amastigotes of T. cruzi I strains may display greater infectivity than metacyclic trypomastigotes towards cultured cell lines as well as target cells that have modified expression of different classes of cellular components. Cultured host cells harboring the bacterium Coxiella burnetii allowed us to gain new insights into the trafficking properties of the different infective forms of T. cruzi, disclosing unexpected requirements for the parasite to transit between the parasitophorous vacuole to its final destination in the host cell cytoplasm.

scholarly journals Cell Adhesion and Ca2+ Signaling Activity in Stably Transfected Trypanosoma cruzi Epimastigotes Expressing the Metacyclic Stage-Specific Surface Molecule gp82

2003 ◽  
Vol 71 (3) ◽  
pp. 1561-1565 ◽  
Author(s):  
Patricio M. Manque ◽  
Ivan Neira ◽  
Vanessa D. Atayde ◽  
Esteban Cordero ◽  
Alice T. Ferreira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Invasion ◽  
Hela Cells ◽  
Plasmid Vector ◽  
Surface Glycoprotein ◽  
Target Cells ◽  
Developmentally Regulated ◽  
Intracellular Ca ◽  
Tyrosine Phosphorylated Protein ◽  
Metacyclic Trypomastigote

ABSTRACT Metacyclic trypomastigotes of Trypanosoma cruzi express a developmentally regulated 82-kDa surface glycoprotein (gp82) that has been implicated in host cell invasion. gp82-mediated interaction of metacyclic forms with target cells induces in both cells activation of the signal transduction pathways, leading to intracellular Ca2+ mobilization, which is required for parasite internalization. Noninfective epimastigotes do not express detectable levels of gp82 and are unable to induce a Ca2+ response. We stably transfected epimastigotes with a T. cruzi expression vector carrying the metacyclic stage gp82 cDNA. These transfectants produced a functional gp82, which bound to and triggered a Ca2+ response in HeLa cells, in the same manner as the metacyclic trypomastigote gp82. Such properties were not found in epimastigotes transfected with the plasmid vector alone. Epimastigotes expressing gp82 on the surface adhered to HeLa cells but were not internalized. Treatment of gp82-expressing epimastigotes with forskolin, an activator of adenylyl cyclase that increases the metacyclic trypomastigote entry into target cells, did not promote parasite internalization. P175, an intracellular tyrosine phosphorylated protein, which appears to play a role in gp82-dependent signaling cascade in metacyclic forms, was undetectable in epimastigotes, either transfected or not with pTEX-gp82. Overall, our results indicate that gp82 is required but not sufficient for target cell invasion.

scholarly journals Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Camilla Ioshida Vasconcelos ◽  
A Cronemberger-Andrade ◽  
Normanda Souza-Melo ◽  
Juliana Terzi Maricato ◽  
Patrícia Xander ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Extracellular Vesicles ◽  
Nitrosative Stress ◽  
Environmental Changes ◽  
Stress Conditions ◽  
Host Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Proinflammatory Activity ◽  
Major Surface

All extracellular forms of Trypanosoma cruzi, the causative agent of Chagas disease, release extracellular vesicles (EVs) containing major surface molecules of the parasite. EV release depends on several mechanisms (internal and external). However, most of the environmental conditions affecting this phenomenon are still unknown. In this work, we evaluated EV release under different stress conditions and their ability to be internalized by the parasites. In addition, we investigated whether the release conditions would affect their immunomodulatory properties in preactivated bone marrow-derived macrophages (BMDM). Sodium azide and methyl-cyclo-β-dextrin (CDB) reduced EV release, indicating that this phenomenon relies on membrane organization. EV release was increased at low temperatures (4°C) and acidic conditions (pH 5.0). Under this pH, trypomastigotes differentiated into amastigotes. EVs are rapidly liberated and reabsorbed by the trypomastigotes in a concentration-dependent manner. Nitrosative stress caused by sodium nitrite in acid medium or S-nitrosoglutathione also stimulated the secretion of EVs. EVs released under all stress conditions also maintained their proinflammatory activity and increased the expression of iNOS, Arg 1, IL-12, and IL-23 genes in IFN-γ and LPS preactivated BMDM. In conclusion, our results suggest a budding mechanism of release, dependent on the membrane structure and parasite integrity. Stress conditions did not affect functional properties of EVs during interaction with host cells. EV release variations under stress conditions may be a physiological response against environmental changes.

scholarly journals Good Cholesterol Gone Bad? HDL and COVID-19

2021 ◽  
Vol 22 (19) ◽  
pp. 10182
Author(s):  
George E. G. Kluck ◽  
Jeong-Ah Yoo ◽  
Emmanuel H. Sakarya ◽  
Bernardo L. Trigatti
Keyword(s):  
Cholesterol Metabolism ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Inverse Correlation ◽  
Host Cells ◽  
Target Cells ◽  
Increased Risk ◽  
Class B ◽  
Low Hdl ◽  
And Function

The transmissible respiratory disease COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide since its first reported outbreak in December of 2019 in Wuhan, China. Since then, multiple studies have shown an inverse correlation between the levels of high-density lipoprotein (HDL) particles and the severity of COVID-19, with low HDL levels being associated with an increased risk of severe outcomes. Some studies revealed that HDL binds to SARS-CoV-2 particles via the virus’s spike protein and, under certain conditions, such as low HDL particle concentrations, it facilitates SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) and infection of host cells. Other studies, however, reported that HDL suppressed SARS-CoV-2 infection. In both cases, the ability of HDL to enhance or suppress virus infection appears to be dependent on the expression of the HDL receptor, namely, the Scavenger Receptor Class B type 1 (SR-B1), in the target cells. SR-B1 and HDL represent crucial mediators of cholesterol metabolism. Herein, we review the complex role of HDL and SR-B1 in SARS-CoV-2-induced disease. We also review recent advances in our understanding of HDL structure, properties, and function during SARS-CoV-2 infection and the resulting COVID-19 disease.

scholarly journals Actin Cytoskeleton-Dependent and -Independent Host Cell Invasion by Trypanosoma cruzi Is Mediated by Distinct Parasite Surface Molecules

2006 ◽  
Vol 74 (10) ◽  
pp. 5522-5528 ◽  
Author(s):  
Daniele Ferreira ◽  
Mauro Cortez ◽  
Vanessa D. Atayde ◽  
Nobuko Yoshida
Keyword(s):  
Trypanosoma Cruzi ◽  
Actin Cytoskeleton ◽  
Host Cell ◽  
Cell Invasion ◽  
Hela Cells ◽  
Cytochalasin D ◽  
Target Cells ◽  
Host Cell Invasion ◽  
Latrunculin B ◽  
Surface Molecules

ABSTRACT The disassembly of host cell actin cytoskeleton as a facilitator of Trypanosoma cruzi invasion has been reported by some authors, while other workers claim that it instead inhibits internalization of the parasite. In this study we aimed at elucidating the basis of this discrepancy. We performed experiments with metacyclic trypomastigotes of T. cruzi strains G and CL, which differ markedly in infectivity and enter target cells by engaging the surface molecules gp35/50 and gp82, respectively, which have signaling activity. Treatment of HeLa cells with the F-actin-disrupting drug cytochalasin D or latrunculin B inhibited the invasion by strain G but not the invasion by strain CL. In contrast to cells penetrated by strain CL, which were previously shown to have a disrupted actin cytoskeleton architecture, no such alteration was observed in HeLa cells invaded by strain G, and parasites were found to be closely associated with target cell actin. Coinfection with enteroinvasive Escherichia coli (EIEC), which recruits host cell actin for internalization, drastically reduced entry of strain CL into HeLa cells but not entry of strain G. In contrast to gp82 in its recombinant form, which induces disruption of F-actin and inhibits EIEC invasion, purified mucin-like gp35/50 molecules promoted an increase in EIEC uptake by HeLa cells. These data, plus the finding that drugs that interfere with mammalian cell signaling differentially affect the internalization of metacyclic forms of strains G and CL, indicate that the host cell invasion mediated by gp35/50 is associated with signaling events that favor actin recruitment, in contrast to gp82-dependent invasion, which triggers the signaling pathways leading to disassembly of F-actin.

scholarly journals Cytotoxic T-Lymphocyte-Mediated Lysis ofToxoplasma gondii-Infected Target Cells Does Not Lead to Death of Intracellular Parasites

1998 ◽  
Vol 66 (10) ◽  
pp. 4651-4655 ◽  
Author(s):  
Keizo Yamashita ◽  
Katsuyuki Yui ◽  
Masakatsu Ueda ◽  
Akihiko Yano
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Host Cells ◽  
Target Cells ◽  
Intracellular Pathogen ◽  
Competitive Pcr ◽  
Gene Encoding ◽  
Intracellular Parasites ◽  
Major Surface ◽  
Dna Template

ABSTRACT CD8+ T cells play a crucial role in the control of infection with intracellular microbes. The mechanisms underlying the CD8+ T-cell-mediated clearance of the intracellular pathogen Toxoplasma gondii are, however, not completely understood. The effect of CD8+ cytotoxic T-lymphocyte (CTL)-mediated lysis of host cells on the viability of intracellular T. gondii was investigated. Quantitative competitive PCR of the gene encoding T. gondii major surface antigen (SAG-1) was combined with treatment of the parasites with DNase, which removed the DNA template of nonviable parasites. The induction by CD8+ CTLs of apoptosis in cells infected withT. gondii did not result in the reduction of live parasites, indicating that intracellular T. gondii remains alive after lysis of host cells by CTLs.

scholarly journals Mechanisms Associated with Trypanosoma cruzi Host Target Cell Adhesion, Recognition and Internalization

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 534
Author(s):  
Oscar Hernán Rodríguez-Bejarano ◽  
Catalina Avendaño ◽  
Manuel Alfonso Patarroyo
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
Mammalian Host ◽  
Target Cells ◽  
Cell Plasma ◽  
Insect Bites ◽  
Host Target

Chagas disease is caused by the kinetoplastid parasite Trypanosoma cruzi, which is mainly transmitted by hematophagous insect bites. The parasite’s lifecycle has an obligate intracellular phase (amastigotes), while metacyclic and bloodstream-trypomastigotes are its infective forms. Mammalian host cell recognition of the parasite involves the interaction of numerous parasite and host cell plasma membrane molecules and domains (known as lipid rafts), thereby ensuring internalization by activating endocytosis mechanisms triggered by various signaling cascades in both host cells and the parasite. This increases cytoplasmatic Ca2+ and cAMP levels; cytoskeleton remodeling and endosome and lysosome intracellular system association are triggered, leading to parasitophorous vacuole formation. Its membrane becomes modified by containing the parasite’s infectious form within it. Once it has become internalized, the parasite seeks parasitophorous vacuole lysis for continuing its intracellular lifecycle, fragmenting such a vacuole’s membrane. This review covers the cellular and molecular mechanisms involved in T. cruzi adhesion to, recognition of and internalization in host target cells.

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