High-Definition DIC Imaging Uncovers Transient Stages of Pathogen Infection Cycles on the Surface of Human Adult Stem Cell-Derived Intestinal Epithelium

Rijn, Jorik M. van; Eriksson, Jens; Grüttner, Jana; Sundbom, Magnus; Webb, Dominic-Luc; Hellström, Per M.; Svärd, Staffan G.; Sellin, Mikael E.

doi:10.1128/mbio.00022-22

Cited by 14 publications

(35 citation statements)

References 92 publications

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“…One interesting observation in this study is that Giardia cysts and encysting cell/trophozoite cell debris induce a very strong response in the Caco-2 cells and this can reflect that Giardia , even if it is mainly colonizing the duodenum, can give effects on host responses in the lower part of the intestinal region and this has been seen in earlier in vivo studies ( Cotton et al., 2014 ; Allain & Buret, 2020 ). New systems using non-transformed cells are needed in order to further study interactions between Giardia and host cells and the recent publication of two studies of Giardia -host cell interactions using enteroids derived from human intestinal stem cells show that this is on the way ( Holthaus et al., 2021 ; van Rijn et al., 2022 ). In these systems it will be important to include parasites or antigens from all life cycle stages of Giardia in order to get a complete picture of Giardia ’s molecular pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Dual RNA Sequencing Reveals Key Events When Different Giardia Life Cycle Stages Interact With Human Intestinal Epithelial Cells In Vitro

Rojas

Grüttner

Ma’ayeh

et al. 2022

Front. Cell. Infect. Microbiol.

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Giardia intestinalis is a protozoan parasite causing diarrheal disease, giardiasis, after extracellular infection of humans and other mammals’ intestinal epithelial cells (IECs) of the upper small intestine. The parasite has two main life cycle stages: replicative trophozoites and transmissive cysts. Differentiating parasites (encysting cells) and trophozoites have recently been shown to be present in the same regions of the upper small intestine, whereas most mature cysts are found further down in the intestinal system. To learn more about host-parasite interactions during Giardia infections, we used an in vitro model of the parasite’s interaction with host IECs (differentiated Caco-2 cells) and Giardia WB trophozoites, early encysting cells (7 h), and cysts. Dual RNA sequencing (Dual RNAseq) was used to identify differentially expressed genes (DEGs) in both Giardia and the IECs, which might relate to establishing infection and disease induction. In the human cells, the largest gene expression changes were found in immune and MAPK signaling, transcriptional regulation, apoptosis, cholesterol metabolism and oxidative stress. The different life cycle stages of Giardia induced a core of similar DEGs but at different levels and there are many life cycle stage-specific DEGs. The metabolic protein PCK1, the transcription factors HES7, HEY1 and JUN, the peptide hormone CCK and the mucins MUC2 and MUC5A are up-regulated in the IECs by trophozoites but not cysts. Cysts specifically induce the chemokines CCL4L2, CCL5 and CXCL5, the signaling protein TRKA and the anti-bacterial protein WFDC12. The parasite, in turn, up-regulated a large number of hypothetical genes, high cysteine membrane proteins (HCMPs) and oxidative stress response genes. Early encysting cells have unique DEGs compared to trophozoites (e.g. several uniquely up-regulated HCMPs) and interaction of these cells with IECs affected the encystation process. Our data show that different life cycle stages of Giardia induce different gene expression responses in the host cells and that the IECs in turn differentially affect the gene expression in trophozoites and early encysting cells. This life cycle stage-specific host-parasite cross-talk is an important aspect to consider during further studies of Giardia’s molecular pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Dual RNA Sequencing Reveals Key Events When Different Giardia Life Cycle Stages Interact With Human Intestinal Epithelial Cells In Vitro

Rojas

Grüttner

Ma’ayeh

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Recent studies on human intestinal organoids showed that STm induced pro-inflammatory gene expression and downregulation of genes associated with cell cycle and DNA repair affecting the host proliferation machinery ( Lawrence et al, 2021 ). Besides the 3D organoid model, 2D organoid monolayer model allow imaging of infection and interaction between IECs and STm as well as the importance of M cells providing an interesting tool to identify STm interaction with specific IEC ( Nickerson et al, 2021 ; van Rijn et al, 2022 ).…”

Section: Relevance Of Intestinal Epithelial Organoids To Decipher ...mentioning

confidence: 99%

Cross-Talk Between the Intestinal Epithelium and Salmonella Typhimurium

et al. 2022

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Salmonella enterica serovars are invasive gram-negative bacteria, causing a wide range of diseases from gastroenteritis to typhoid fever, representing a public health threat around the world. Salmonella gains access to the intestinal lumen after oral ingestion of contaminated food or water. The crucial initial step to establish infection is the interaction with the intestinal epithelium. Human-adapted serovars such as S. Typhi or S. Paratyphi disseminate to systemic organs and induce life-threatening disease known as typhoid fever, whereas broad-host serovars such as S. Typhimurium usually are limited to the intestine and responsible for gastroenteritis in humans. To overcome intestinal epithelial barrier, Salmonella developed mechanisms to induce cellular invasion, intracellular replication and to face host defence mechanisms. Depending on the serovar and the respective host organism, disease symptoms differ and are linked to the ability of the bacteria to manipulate the epithelial barrier for its own profit and cross the intestinal epithelium.This review will focus on S. Typhimurium (STm). To better understand STm pathogenesis, it is crucial to characterize the crosstalk between STm and the intestinal epithelium and decipher the mechanisms and epithelial cell types involved. Thus, the purpose of this review is to summarize our current knowledge on the molecular dialogue between STm and the various cell types constituting the intestinal epithelium with a focus on the mechanisms developed by STm to cross the intestinal epithelium and access to subepithelial or systemic sites and survive host defense mechanisms.

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“…Murine small intestinal enteroid cultures were thawed from previously established stocks (Hausmann et al, 2020), and maintained within Matrigel (Corning) domes overlaid with complete mouse IntestiCult (Stemcell), as detailed elsewhere (Samperio Ventayol et al, 2021). Enteroid-derived monolayers were established using an adapted version of a recently developed 3D-printed polylactide (PLA) transwell chamber, allowing a short working distance for dipping-objective microscopy (van Rijn et al, 2022).…”

Section: Murine Enteroid-derived Epithelial Monolayersmentioning

confidence: 99%

A motile doublet form of Salmonella Typhimurium diversifies target search behavior at the epithelial surface

Fattinger

Florbrant

et al. 2022

Molecular Microbiology

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High-Definition DIC Imaging Uncovers Transient Stages of Pathogen Infection Cycles on the Surface of Human Adult Stem Cell-Derived Intestinal Epithelium

Cited by 14 publications

References 92 publications

Dual RNA Sequencing Reveals Key Events When Different Giardia Life Cycle Stages Interact With Human Intestinal Epithelial Cells In Vitro

Dual RNA Sequencing Reveals Key Events When Different Giardia Life Cycle Stages Interact With Human Intestinal Epithelial Cells In Vitro

Cross-Talk Between the Intestinal Epithelium and Salmonella Typhimurium

A motile doublet form of Salmonella Typhimurium diversifies target search behavior at the epithelial surface

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