Giardia's Epithelial Cell Interaction In Vitro: Mimicking Asymptomatic Infection?

Abstract

The protozoan parasite Giardia duodenalis is responsible for more than 280 million cases of gastrointestinal complaints (“giardiasis”) every year, worldwide. Infections are acquired orally, mostly via uptake of cysts in contaminated drinking water. After transformation into the trophozoite stage, parasites start to colonize the duodenum and upper jejunum where they attach to the intestinal epithelium and replicate vegetatively. Outcome of Giardia infections vary between individuals, from self-limiting to chronic, and asymptomatic to severely symptomatic infection, with unspecific gastrointestinal complaints. One proposed mechanism for pathogenesis is the breakdown of intestinal barrier function. This has been studied by analyzing trans-epithelial electric resistances (TEER) or by indicators of epithelial permeability using labeled sugar compounds in in vitro cell culture systems, mouse models or human biopsies and epidemiological studies. Here, we discuss the results obtained mainly with epithelial cell models to highlight contradictory findings. We relate published studies to our own findings that suggest a lack of barrier compromising activities of recent G. duodenalis isolates of assemblage A, B, and E in a Caco-2 model system. We propose that this epithelial cell model be viewed as mimicking asymptomatic infection. This view will likely lead to a more informative use of the model if emphasis is shifted from aiming to identify Giardia virulence factors to defining non-parasite factors that arguably appear to be more decisive for disease.

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions

“…Most of this data has been generated using different in vitro models of giardiasis using human or rat intestinal epithelial cell-lines combined with trophozoites or parasite extracts and it has been complemented by experimental infections in mice, gerbils and data from human giardiasis patients (Emery-Corbin et al, 2020;Jex et al, 2020). Various strategies have been developed to study the interplay and the outcome of interaction between Giardia and host cell in vitro and in vivo (Roxström-Lindquist et al, 2005;Ringqvist et al, 2011;Ferella et al, 2014;Kraft et al, 2017;Ma'ayeh et al, 2017). Here, we have used our well-characterized in vitro model of interaction between differentiated Caco-2 cells and G. intestinalis WB trophozoites (Roxström-Lindquist et al, 2005) combined with RNA sequencing to study transcriptional changes in trophozoites during the early hours of co-incubation with the human cells.…”

In vitro and ex vivo evaluation of the anti-Giardia duodenalis activity of the supernatant of Slab51 (SivoMixx)

“…In previous studies, a variety of different systems have been used to evaluate the adherence and growth of G . duodenalis , including synthetic surfaces, human cells and non-human cells, as isolated rat enterocytes and rat enterocyte cell lines [35–37]. Among them, the human colonic adenocarcinoma derived epithelial cell line Caco-2, functionally and structurally may resemble small bowel enterocytes [38].…”

The role of innate lymphoid cells in response to microbes at mucosal surfaces

“…153 The protozoan Giardia lamblia is an extracellular pathogen found worldwide that causes giardiasis, a disease that is associated with gastrointestinal malfunction. 154 This infection mostly occurs via oral uptake of G. lamblia cysts in contaminated drinking water. Following oral infection, G. lamblia colonizes the small intestine where the organism attaches to the intestinal epithelium, replicates vegetatively and disrupts intestinal barrier function.…”