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.

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 Inhibition of Trypanosoma cruzi growth in mammalian cells by purine and pyrimidine analogs.

1996 ◽  
Vol 40 (11) ◽  
pp. 2455-2458 ◽  
Author(s):  
J Nakajima-Shimada ◽  
Y Hirota ◽  
T Aoki
Keyword(s):  
Trypanosoma Cruzi ◽  
Growth Inhibition ◽  
Host Cell ◽  
Culture System ◽  
Mammalian Cells ◽  
Screening Method ◽  
Host Cells ◽  
Mammalian Host ◽  
Dependent Manner ◽  
Pyrimidine Analogs

Trypanosoma cruzi, the causative agent of Chagas' disease, exhibits two different developmental stages in mammals, the amastigote, an intracellular form that proliferates in the cytoplasm of host cells, and the trypomastigote, an extracellular form that circulates in the bloodstream. We have already established an in vitro culture system using mammalian host cells (HeLa) infected with T. cruzi in which the time course of parasite growth is determined quantitatively. We adopted this system for the screening of anti-T. cruzi agents that would ideally prove to be effective against trypanosomes with no toxicity to the host cell. Of the purine analogs tested, allopurinol markedly inhibited the growth of amastigotes in a dose-dependent manner, with no lethal effect on trypomastigotes. 3'-Deoxyinosine and 3'-deoxyadenosine also suppressed T. cruzi growth inside the host cell, with the concentrations causing 50% growth inhibition being 10 and 5 microM, respectively, in contrast to a concentration causing 50% growth inhibition of 3 microM for allopurinol. Among the pyrimidine analogs examined, 3'-azido-3'-deoxythymidine (zidovudine) significantly reduced the growth of the parasite at concentrations as low as 1 microM. The anti-human immunodeficiency virus agents 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine caused a decrease in amastigote growth, while 2',3'-dideoxycytidine and 2',3'-dideoxyuridine had no inhibitory effect. When Swiss 3T3 fibroblasts were used as host cells, allopurinol, 3'-deoxyinosine, 3'-deoxyadenosine, and 3'-azid-3'-deoxythymidine also markedly inhibited T. cruzi proliferation. These results indicate that our culture system is useful as a primary screening method for candidate compounds against T. cruzi on the basis of two criteria, namely, intracellular replication by the parasite and host-cell infection rate.

scholarly journals Molecular Dissection of the Campylobacter jejuni CadF and FlpA Virulence Proteins in Binding to Host Cell Fibronectin

2020 ◽  
Vol 8 (3) ◽  
pp. 389 ◽  
Author(s):  
Prabhat K. Talukdar ◽  
Nicholas M. Negretti ◽  
Kyrah L. Turner ◽  
Michael E. Konkel
Keyword(s):  
Host Cell ◽  
Campylobacter Jejuni ◽  
Mapk Signaling ◽  
Effector Proteins ◽  
Host Cells ◽  
Target Cells ◽  
Cell Binding ◽  
Virulence Proteins ◽  
Host Target ◽  
Cell Signaling Pathways

Campylobacter jejuni, a zoonotic pathogen that frequently colonizes poultry, possesses two Microbial Surface Components Recognizing Adhesive Matrix Molecule(s) (MSCRAMMs) termed CadF and FlpA that bind to the glycoprotein fibronectin (FN). Previous to this study, it was not known whether the CadF and FlpA proteins were functionally redundant or if both were required to potentiate host cell binding and signaling processes. We addressed these questions by generating a complete repertoire of cadF and flpA mutants and complemented isolates, and performing multiple phenotypic assays. Both CadF and FlpA were found to be necessary for the maximal binding of C. jejuni to FN and to host cells. In addition, both CadF and FlpA are required for the delivery of the C. jejuni Cia effector proteins into the cytosol of host target cells, which in turn activates the MAPK signaling pathway (Erk 1/2) that is required for the C. jejuni invasion of host cells. These data demonstrate the non-redundant and bi-functional nature of these two C. jejuni FN-binding proteins. Taken together, the C. jejuni CadF and FlpA adhesins facilitate the binding of C. jejuni to the host cells, permit delivery of effector proteins into the cytosol of a host target cell, and aid in the rewiring of host cell signaling pathways to alter host cell behavior.

scholarly journals Characterization of Sec-Translocon-Dependent Extracytoplasmic Proteins of Rickettsia typhi

2008 ◽  
Vol 190 (18) ◽  
pp. 6234-6242 ◽  
Author(s):  
Nicole C. Ammerman ◽  
M. Sayeedur Rahman ◽  
Abdu F. Azad
Keyword(s):  
Host Cell ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Transcriptional Analysis ◽  
Mammalian Host ◽  
Signal Peptides ◽  
Cell Infection ◽  
Rickettsia Typhi ◽  
Sec Translocon

ABSTRACT As obligate intracellular, vector-borne bacteria, rickettsiae must adapt to both mammalian and arthropod host cell environments. Deciphering the molecular mechanisms of the interactions between rickettsiae and their host cells has largely been hindered by the genetic intractability of these organisms; however, research in other gram-negative pathogens has demonstrated that many bacterial determinants of attachment, entry, and pathogenesis are extracytoplasmic proteins. The annotations of several rickettsial genomes indicate the presence of homologs of the Sec translocon, the major route for bacterial protein secretion from the cytoplasm. For Rickettsia typhi, the etiologic agent of murine typhus, homologs of the Sec-translocon-associated proteins LepB, SecA, and LspA have been functionally characterized; therefore, the R. typhi Sec apparatus represents a mechanism for the secretion of rickettsial proteins, including virulence factors, into the extracytoplasmic environment. Our objective was to characterize such Sec-dependent R. typhi proteins in the context of a mammalian host cell infection. By using the web-based programs LipoP, SignalP, and Phobius, a total of 191 R. typhi proteins were predicted to contain signal peptides targeting them to the Sec translocon. Of these putative signal peptides, 102 were tested in an Escherichia coli-based alkaline phosphatase (PhoA) gene fusion system. Eighty-four of these candidates exhibited signal peptide activity in E. coli, and transcriptional analysis indicated that at least 54 of the R. typhi extracytoplasmic proteins undergo active gene expression during infections of HeLa cells. This work highlights a number of interesting proteins possibly involved in rickettsial growth and virulence in mammalian cells.

Trypanosoma cruzi does not induce apoptosis in murine fibroblasts

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 167-175 ◽  
Author(s):  
R. K. CLARK ◽  
R. E. KUHN
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Apoptosis ◽  
Membrane Integrity ◽  
Host Cells ◽  
Mammalian Host ◽  
Host Cell Apoptosis ◽  
Intracellular Parasites ◽  
Murine Fibroblasts ◽  
Infected Cells

The intracellular cycle of Trypanosoma cruzi in mammalian host cells involves the differentiation of dividing amastigote forms into flagellated trypomastigote forms. The mechanism(s) regulating the growth and differentiation of the intracellular parasites is (are) not known. The number of parasites in infected cells can be several hundred and may be enough to induce apoptosis, a suicide-like death programme, generating products (e.g. nuclear proteins) that could function as signals to initiate the differentiation of amastigotes into trypomastigotes. Murine fibroblasts infected with T. cruzi were examined during a 5-day course of infection for evidence of apoptosis. However, characteristics of apoptosis, including degeneration of nuclear structure, condensation of chromatin, loss of plasma membrane integrity, or the cleavage of DNA into nucleosomal fragments, were not observed. Therefore, it is unlikely that products resulting from host cell apoptosis function to induce parasite differentiation. The possibility that T. cruzi might inhibit host cell apoptosis by increasing intracellular levels of Bcl-2, an endogenous inhibitor of apoptosis, was then investigated. Analysis of infected cells by flow cytometry did not demonstrate a significant amount of intracellular Bcl-2. This suggests that if the parasite is inhibiting host cell apoptosis, it is by a method that does not involve increasing levels of Bcl-2.

scholarly journals Evidence for Host Cells as the Major Contributor of Lipids in the Intravacuolar Network of Toxoplasma-Infected Cells

2011 ◽  
Vol 10 (8) ◽  
pp. 1095-1099 ◽  
Author(s):  
Carolina E. Caffaro ◽  
John C. Boothroyd
Keyword(s):  
Host Cell ◽  
Fluorescence Recovery After Photobleaching ◽  
Parasitophorous Vacuole ◽  
Dense Granule ◽  
Host Cells ◽  
Cell Plasma Membrane ◽  
Content Type ◽  
Cell Plasma ◽  
Continuous Stream ◽  
Infected Cells

ABSTRACT The intracellular parasite Toxoplasma gondii develops inside a parasitophorous vacuole (PV) that derives from the host cell plasma membrane during invasion. Previous electron micrograph images have shown that the membrane of this vacuole undergoes an extraordinary remodeling with an extensive network of thin tubules and vesicles, the intravacuolar network (IVN), which fills the lumen of the PV. While dense granule proteins, secreted during and after invasion, are the main factors for the organization and tubulation of the network, little is known about the source of lipids used for this remodeling. By selectively labeling host cell or parasite membranes, we uncovered evidence that strongly supports the host cell as the primary, if not exclusive, source of lipids for parasite IVN remodeling. Fluorescence recovery after photobleaching (FRAP) microscopy experiments revealed that lipids are surprisingly dynamic within the parasitophorous vacuole and are continuously exchanged or replenished by the host cell. The results presented here suggest a new model for development of the parasitophorous vacuole whereby the host provides a continuous stream of lipids to support the growth and maturation of the PVM and IVN.

scholarly journals The Nascent Parasitophorous Vacuole Membrane of Encephalitozoon cuniculi Is Formed by Host Cell Lipids and Contains Pores Which Allow Nutrient Uptake

2008 ◽  
Vol 7 (6) ◽  
pp. 1001-1008 ◽  
Author(s):  
Karin Rönnebäumer ◽  
Uwe Gross ◽  
Wolfgang Bohne
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Fluorescent Dyes ◽  
Parasitophorous Vacuole ◽  
Time Lapse ◽  
Host Cells ◽  
Encephalitozoon Cuniculi ◽  
Invasion Mechanism ◽  
Cell Plasma ◽  
Metabolite Exchange

ABSTRACT Microsporidia are obligate intracellular pathogens which enter host cells by the discharge of a hollow tube through which the sporoplasma is extruded into the host cell. Since this invasion mechanism is very different from common entry strategies, the formation of the parasitophorous vacuole (PV) in Encephalitozoon species is likely to be distinct from known principles. We investigated the origin of the nascent Encephalitozoon cuniculi PV membrane with the aid of fluorescent lipid probes. When Bodipy 500/510-C12-HPC-labeled spores were used for infection, the emerging PV membrane was unlabeled, suggesting that sporoplasma-derived lipids do not significantly contribute to the formation of the PV membrane. In contrast, when raft and nonraft microdomains of the host cell plasma membrane were selectively labeled with DiIC16 and Speedy DiO, both tracers were detectable in the nascent PV membrane shortly after infection, indicating that the bulk lipids of the PV membrane are host cell derived. Time-lapse fluorescence microscopy revealed that the formation of the PV membrane is a fast event (<1.3 s), which occurred simultaneously with the extrusion of the sporoplasma. The portion of the discharged tube which is in contact with the host cell was found to be coated with labeled host cell lipids, which might be an indication for a plasma membrane invagination at the contact site. To investigate the presence of pores in the E. cuniculi PV membrane, we microinjected fluorescent dyes of different sizes into infected host cells. A 0.5-kDa dextran as well as 0.8- to 1.1-kDa peptides could rapidly enter the PV, while a 10-kDa dextran was stably excluded from the PV lumen, indicating that the PV membrane possesses pores with an exclusion size of <10 kDa, which should allow metabolite exchange.

scholarly journals Mixed signals – how Trypanosoma cruzi exploits host-cell communication and signaling to establish infection

2021 ◽  
Vol 134 (5) ◽  
pp. jcs255687
Author(s):  
Carlos Acides Nájera ◽  
Marina Ferreira Batista ◽  
Isabela Meneghelli ◽  
Diana Bahia
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Mammalian Species ◽  
Cell Communication ◽  
Host Cells ◽  
Host Recognition ◽  
Initial Contact ◽  
Host Signaling ◽  
Cytoskeletal Rearrangements

ABSTRACTChagas disease (American trypanosomiasis) is a ‘neglected’ pathology that affects millions of people worldwide, mainly in Latin America. Trypanosoma cruzi, the causative agent, is an obligate intracellular parasite with a complex and diverse biology that infects several mammalian species, including humans. Because of genetic variability among strains and the presence of four biochemically and morphologically distinct parasite forms, the outcome of T. cruzi infection varies considerably depending on host cell type and parasite strain. During the initial contact, cellular communication is established by host-recognition-mediated responses, followed by parasite adherence and penetration. For this purpose, T. cruzi expresses a variety of proteins that modify the host cell, enabling it to safely reach the cytoplasm. After entry into the host cell, T. cruzi forms a transitory structure termed ‘parasitophorous vacuole’ (PV), followed by its cytoplasmic replication and differentiation after PV rupture, and subsequent invasion of other cells. The success of infection, maintenance and survival inside host cells is facilitated by the ability of T. cruzi to subvert various host signaling mechanisms. We focus in this Review on the various mechanisms that induce host cytoskeletal rearrangements, activation of autophagy-related proteins and crosstalk among major immune response regulators, as well as recent studies on the JAK-STAT pathway.

Secretion by Toxoplasma gondii of an antigen that appears to become associated with the parasitophorous vacuole membrane upon invasion of the host cell

1987 ◽  
Vol 88 (2) ◽  
pp. 231-239
Author(s):  
I. Kimata ◽  
K. Tanabe
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Anterior Part ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
Immunoperoxidase Staining ◽  
Cell Plasma ◽  
Sds Page ◽  
Infected Cells ◽  
Triton X

Monoclonal antibodies against Toxoplasma gondii were prepared to characterize antigens of the parasite. Immunoperoxidase staining of parasites fixed with paraformaldehyde and glutaraldehyde (PFAGA) followed by Triton X-100 treatment showed that the antibody of clone I-63 recognized an antigen located in the anterior part of the parasite. When analysed by SDS-PAGE and immunoblotting, the antigen migrated in a 66 × 10(3) Mr region. The parasite antigen diminished greatly in parasites after invasion of host cells, but reappeared around a time when intracellular T. gondii multiplied. Immunodetection on PFAGA-fixed T. gondii-infected cells, whose membranes were permeabilized by freeze-thawing in the presence of 5% glycerol, demonstrated that, immediately after parasite invasion, the I-63 antibody-reactive antigen appeared to become associated with the parasitophorous vacuole (PV) membrane, that had been formed mainly by invagination of the host-cell plasma membrane so as to surround an invading parasite. The antigen remained associated with the PV membrane for some time, but disappeared later when the PV increased in size after the parasites had multiplied several times. These results were strengthened by immunoelectron microscopic observations: the antigen that had been localized at the anterior part of the parasite before invasion appeared in an area of the host cell cytoplasm around the tips of penetrating parasites and, thereafter, extended throughout the surface of the PV membrane when parasites completed invasion. Thus, it appears that the I-63-reactive antigen is secreted by T. gondii upon invasion of the host cell and becomes associated with the PV membrane shortly after invasion.

scholarly journals Trichomonas vaginalis extracellular vesicles are internalized by host cells using proteoglycans and caveolin-dependent endocytosis

2019 ◽  
Vol 116 (43) ◽  
pp. 21354-21360 ◽  
Author(s):  
Anand Kumar Rai ◽  
Patricia J. Johnson
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Trichomonas Vaginalis ◽  
Host Cells ◽  
Titration Calorimetry ◽  
Mammalian Host ◽  
Target Cells ◽  
Host Cell Surface

Trichomonas vaginalis, a human-infective parasite, causes the most prevalent nonviral sexually transmitted infection worldwide. This pathogen secretes extracellular vesicles (EVs) that mediate its interaction with host cells. Here, we have developed assays to study the interface between parasite EVs and mammalian host cells and to quantify EV internalization by mammalian cells. We show that T. vaginalis EVs interact with glycosaminoglycans on the surface of host cells and specifically bind to heparan sulfate (HS) present on host cell surface proteoglycans. Moreover, competition assays using HS or removal of HS from the host cell surface strongly inhibit EV uptake, directly demonstrating that HS proteoglycans facilitate EV internalization. We identified an abundant protein on the surface of T. vaginalis EVs, 4-α-glucanotransferase (Tv4AGT), and show using isothermal titration calorimetry that this protein binds HS. Tv4AGT also competitively inhibits EV uptake, defining it as an EV ligand critical for EV internalization. Finally, we demonstrate that T. vaginalis EV uptake is dependent on host cell cholesterol and caveolin-1 and that internalization proceeds via clathrin-independent, lipid raft-mediated endocytosis. These studies reveal mechanisms used to drive host:pathogen interactions and further our understanding of how EVs are internalized by target cells to allow cross-talk between different cell types.

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