Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection

Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these di...

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Bibliographic Details
Published in:PLoS pathogens 2023-05, Vol.19 (5), p.e1011372-e1011372
Main Authors: Grüttner, Jana, van Rijn, Jorik M, Geiser, Petra, Florbrant, Alexandra, Webb, Dominic-Luc, Hellström, Per M, Sundbom, Magnus, Sellin, Mikael E, Svärd, Staffan G
Format: Article
Language:English
Subjects:
Analysis
Animals
Asymptomatic
Biology and Life Sciences
Biotechnology industry
Cancer
Chemokines
Chronic fatigue syndrome
Development and progression
Diagnosis
Epithelial cells
Epithelial Cells - metabolism
Epithelium
Fitness
Gene expression
Gene sequencing
Giardia
Giardia intestinalis
Giardia lamblia
Giardia lamblia - metabolism
Giardiasis
Giardiasis - metabolism
Host-parasite relationships
Humans
Infection
Infections
Inflammation
Intestine
Intestines
Kinases
Mammals
Medicine and Health Sciences
Microscopy
Parasites
Physiological aspects
Protozoa
RNA
Salmonella
Small intestine
Transcription
Trophozoites
Trophozoites - metabolism
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Summary:Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to G. intestinalis trophozoites, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, "non-fit" or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, "fit" trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active G. intestinalis suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and G. intestinalis gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how G. intestinalis infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1011372