Development of caecaloids to study host–pathogen interactions: new insights into immunoregulatory functions of Trichuris muris extracellular vesicles in the caecum

Duque-Correa, María A.; Schreiber, Fernanda; Rodgers, Faye H.; Goulding, David; Forrest, Sally; White, Ruby; Buck, Amy H.; Grencis, Richard K.; Berriman, Matthew

doi:10.1016/j.ijpara.2020.06.001

Cited by 26 publications

(20 citation statements)

References 62 publications

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“…Consequently, organoids have enabled previously unseen progress in many fields, one of them being infection biology, in particular for bacteria and viruses [reviewed in Hill and Spence (2017) and Artegiani and Clevers (2018) ]. The organoid model has enabled advances in the field of parasitology with infection studies on Cryptosporidium ( Heo et al, 2018 ; Wilke et al, 2019 ), T. gondii ( Derricott et al, 2019 ; Luu et al, 2019 ; Martorelli Di Genova et al, 2019 ), G. duodenalis ( Kraft et al, 2020 ) and helminths ( Eichenberger et al, 2018 ; Duque-Correa et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Harmonization of Protocols for Multi-Species Organoid Platforms to Study the Intestinal Biology of Toxoplasma gondii and Other Protozoan Infections

Holthaus

Delgado-Betancourt

Aebischer

et al. 2021

Front. Cell. Infect. Microbiol.

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The small intestinal epithelium is the primary route of infection for many protozoan parasites. Understanding the mechanisms of infection, however, has been hindered due to the lack of appropriate models that recapitulate the complexity of the intestinal epithelium. Here, we describe an in vitro platform using stem cell-derived intestinal organoids established for four species that are important hosts of Apicomplexa and other protozoa in a zoonotic context: human, mouse, pig and chicken. The focus was set to create organoid-derived monolayers (ODMs) using the transwell system amenable for infection studies, and we provide straightforward guidelines for their generation and differentiation from organ-derived intestinal crypts. To this end, we reduced medium variations to an absolute minimum, allowing generation and differentiation of three-dimensional organoids for all four species and the subsequent generation of ODMs. Quantitative RT-PCR, immunolabeling with antibodies against marker proteins as well as transepithelial-electrical resistance (TEER) measurements were used to characterize ODM’s integrity and functional state. These experiments show an overall uniform generation of monolayers suitable for Toxoplasma gondii infection, although robustness in terms of generation of stable TEER levels and cell differentiation status varies from species to species. Murine duodenal ODMs were then infected with T. gondii and/or Giardia duodenalis, two parasites that temporarily co-inhabit the intestinal niche but have not been studied previously in cellular co-infection models. T. gondii alone did not alter TEER values, integrity and transcriptional abundance of tight junction components. In contrast, in G. duodenalis-infected ODMs all these parameters were altered and T. gondii had no apparent influence on the G. duodenalis-triggered phenotype. In conclusion, we provide robust protocols for the generation, differentiation and characterization of intestinal organoids and ODMs from four species. We show their applications for comparative studies on parasite-host interactions during the early phase of a T. gondii infection but also its use for co-infections with other relevant intestinal protozoans.

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Section: Discussionmentioning

confidence: 99%

Harmonization of Protocols for Multi-Species Organoid Platforms to Study the Intestinal Biology of Toxoplasma gondii and Other Protozoan Infections

Holthaus

Delgado-Betancourt

Aebischer

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Recent work has demonstrated the possibility to recapitulate complex life cycles of eukaryotic parasites. This is the case for Cryptosporidium parvum and Trichuris muris, which were studied using adult stem-cell-derived human and mouse intestinal organoids, respectively, grown in 3D (Heo et al, 2018;Duque-Correa et al, 2020). Cryptosporidium parvum could also be studied on intestinal monolayers at an air-liquid interface (Wilke et al, 2019) and had recently been transferred to an intestine-on-a-chip device, paving the way for long-term studies (Nikolaev et al, 2020).…”

Section: Pathogen Replication and Life Cyclementioning

confidence: 99%

Organoids and organs-on-chips: Insights into human gut-microbe interactions

Puschhof

Pleguezuelos-Manzano

Clevers

2021

Cell Host & Microbe

116

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The important and diverse roles of the gut microbiota in human health and disease are increasingly recognized. The difficulty of inferring causation from metagenomic microbiome sequencing studies and from mouse-human interspecies differences has prompted the development of sophisticated in vitro models of human gutmicrobe interactions. Here, we review recent advances in the co-culture of microbes with intestinal and colonic epithelia, comparing the rapidly developing fields of organoids and organs-on-chips with other standard models. We describe how specific individual processes by which microbes and epithelia interact can be recapitulated in vitro. Using examples of bacterial, viral, and parasitic infections, we highlight the advantages of each culture model and discuss current trends and future possibilities to build more complex co-cultures.

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“…Eichenberger et al (2018) showed that T. muris ELVs could be internalized by mouse colonic organoids raising the possibility of the ELVs communicating with intestinal epithelial cells. Duque-Correa et al (2020) developed a novel caecaloid model micro-injected with T. muris adult-derived ELVs which enabled study of the host pathogen interaction in vitro. Their study argues that the caecum is a unique and different niche to the colon and so provides additional and novel data to that provided in Eichenberger et al (2018).…”

Section: Exosomes and Exosome-like Vesiclesmentioning

confidence: 99%