In vitro models for investigation of the host-parasite interface - possible applications in acute Chagas disease

Breyner, Natália Martins; Hecht, Markus; Nitz, Nadjar; Rose, Ester; Carvalho, Juliana Lott

doi:10.1016/j.actatropica.2019.105262

Cited by 11 publications

(10 citation statements)

References 105 publications

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“…Both in vivo and in vitro infection models will be required to study virus-parasite interactions both independently and in association with the human or animal hosts of the parasites [159]. Due to their complex life cycles and culture requirements, for many protozoan parasites such models are still inadequate, incomplete, since they do not replicate all the parasite life stages, do not exist, or might simply not be suited to evaluating virus behaviour [160][161][162][163].…”

Section: Resultsmentioning

confidence: 99%

Viruses of protozoan parasites and viral therapy: Is the time now right?

Barrow

Dujardin

Fasel

et al. 2020

Virol J

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Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

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Section: Resultsmentioning

confidence: 99%

Viruses of protozoan parasites and viral therapy: Is the time now right?

Barrow

Dujardin

Fasel

et al. 2020

Virol J

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“…We found important differences in the OXPHOS response to T. cruzi infection depending on the origin of the infected cell (human or mouse), highlighting in the in vitro studies opposite responses depending on this variable, both at the transcriptomic and functional level. We caution about not considering the genetic and immunological differences between mice and humans before comparing results, and also, we believe that the use of in vitro models that include primary human cells, human induced pluripotent stem cells and 3D cultures (Breyner et al, 2020) are recommended options. Finally, delving into the activation mechanisms of PI3K/AKT would open new perspectives in hostdirected therapies in Chagas disease.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Studies on Trypanosoma cruzi – Host Cell Interactions: A Complex Puzzle of Variables

Libisch

Rego

Robello

2021

Front. Cell. Infect. Microbiol.

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Chagas Disease, caused by the protozoan parasite Trypanosoma cruzi, affects nearly eight million people in the world. T. cruzi is a complex taxon represented by different strains with particular characteristics, and it has the ability to infect and interact with almost any nucleated cell. The T. cruzi-host cell interactions will trigger molecular signaling cascades in the host cell that will depend on the particular cell type and T. cruzi strain, and also on many different experimental variables. In this review we collect data from multiple transcriptomic and functional studies performed in different infection models, in order to highlight key differences between works that in our opinion should be addressed when comparing and discussing results. In particular, we focus on changes in the respiratory chain and oxidative phosphorylation of host cells in response to infection, which depends on the experimental model of T. cruzi infection. Finally, we also discuss host cell responses which reiterate independently of the strain, cell type and experimental conditions.

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“…T. cruzi infection results in Chagas disease, which is the leading cause of myocarditis [ 129 ]. Even though other in vitro models such as immortalised cell lines, primary cell lines and hiPSC-derived cardiomyocytes have been used, there have been outstanding questions, such as the different manifestations and time of onset of Chagas disease myopathy in patients [ 130 ]. In this context, patient-derived cardiac organoids could provide new insight into the pathophysiology of Chagas disease, such as the mechanism underlying T.cruzi persistence.…”

Section: Common Infectious Diseases Modelled By Organoidsmentioning

confidence: 99%

3D Human Organoids: The Next “Viral” Model for the Molecular Basis of Infectious Diseases

2022

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The COVID-19 pandemic has driven the scientific community to adopt an efficient and reliable model that could keep up with the infectious disease arms race. Coinciding with the pandemic, three dimensional (3D) human organoids technology has also gained traction in the field of infectious disease. An in vitro construct that can closely resemble the in vivo organ, organoid technology could bridge the gap between the traditional two-dimensional (2D) cell culture and animal models. By harnessing the multi-lineage characteristic of the organoid that allows for the recapitulation of the organotypic structure and functions, 3D human organoids have emerged as an essential tool in the field of infectious disease research. In this review, we will be providing a comparison between conventional systems and organoid models. We will also be highlighting how organoids played a role in modelling common infectious diseases and molecular mechanisms behind the pathogenesis of causative agents. Additionally, we present the limitations associated with the current organoid models and innovative strategies that could resolve these shortcomings.

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In vitro models for investigation of the host-parasite interface - possible applications in acute Chagas disease

Cited by 11 publications

References 105 publications

Viruses of protozoan parasites and viral therapy: Is the time now right?

Viruses of protozoan parasites and viral therapy: Is the time now right?

Transcriptional Studies on Trypanosoma cruzi – Host Cell Interactions: A Complex Puzzle of Variables

3D Human Organoids: The Next “Viral” Model for the Molecular Basis of Infectious Diseases

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