Gene expression changes during Giardia–host cell interactions in serum-free medium

Ferella, Marcela; Davids, Barbara J.; Cipriano, Michael J.; Birkeland, Shanda R.; Palm, Daniel; Gillin, Frances D.; McArthur, Andrew G.; Svärd, Staffan G.

doi:10.1016/j.molbiopara.2014.09.007

Cited by 18 publications

(30 citation statements)

References 20 publications

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“…This smaller down-regulated protein response suggests the response of Giardia trophozoites to host signals in vitro may be inductive rather than repressive. The dataset size of differentially expressed proteins is similar to those seen previously with HT-29 cells over 6 hours incubation in RNA studies 5 . Although some common differentially expressed proteins were observed, the majority of proteins were expressed uniquely between trophozoites stimulated by host secretions compared to attachment ( Fig.…”

Section: Resultssupporting

confidence: 68%

“…4A ), with 45 proteins differentially expressed in trophozoites co-incubated with IECs ( Table 1 ), and 38 proteins in HSF-exposed trophozoites ( Table 2 ). These included several up-regulated proteins previously identified the transcript level during co-incubation of Giardia trophozoites with IECs 4 5 , including tenascin proteins, cathepsin B precursor, uridine phosphorylase 1 (UPL-1) and thioredoxin. A total of 30 variant-specific surface proteins (VSPs) were also identified in the whole dataset, with eight and four variants up-regulated in HSF and CI treatments, respectively ( Supplementary Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Results indicate that these interaction models are stimulatory, inducing expression of parasite factors which have limited or no expression in axenic culture alone 3 . Additional studies have addressed gene expression and transcriptional changes in Giardia trophozoites co-incubated with Caco-2 and HCT-8 cells 4 , and HT-29 cells 5 , and analysed the secreted proteomes 3 . There have also been complementary studies of transcripts from IECs exposed to Giardia trophozoites 6 7 .…”

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confidence: 99%

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Induction of virulence factors in Giardia duodenalis independent of host attachment

Emery

Mirzaei

Vuong³

et al. 2016

Sci Rep

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Giardia duodenalis is responsible for the majority of parasitic gastroenteritis in humans worldwide. Host-parasite interaction models in vitro provide insights into disease and virulence and help us to understand pathogenesis. Using HT-29 intestinal epithelial cells (IEC) as a model we have demonstrated that initial sensitisation by host secretions reduces proclivity for trophozoite attachment, while inducing virulence factors. Host soluble factors triggered up-regulation of membrane and secreted proteins, including Tenascins, Cathepsin-B precursor, cystatin, and numerous Variant-specific Surface Proteins (VSPs). By comparison, host-cell attached trophozoites up-regulated intracellular pathways for ubiquitination, reactive oxygen species (ROS) detoxification and production of pyridoxal phosphate (PLP). We reason that these results demonstrate early pathogenesis in Giardia involves two independent host-parasite interactions. Motile trophozoites respond to soluble secreted signals, which deter attachment and induce expression of virulence factors. Trophozoites attached to host cells, in contrast, respond by up-regulating intracellular pathways involved in clearance of ROS, thus anticipating the host defence response.

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Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Induction of virulence factors in Giardia duodenalis independent of host attachment

Emery

Mirzaei

Vuong³

et al. 2016

Sci Rep

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“…The persistent translocation of mucosally associated bacterial microbiota has been proposed to explain post-infection irritable bowel syndrome and chronic fatigue [ 31 ], sequelae present in up to 5% of individuals with prior giardiasis [ 136 ], particularly in those whose initial course was more protracted [ 137 ]. Mechanisms by which Giardia could influence microbiota composition include alterations in the luminal nutritional environment as previously stated, as well as dampening the epithelial cell inflammatory responses through post-translational reductions in IL-8 and decreased nitric oxide synthesis [ 102 , 120 , 138 – 140 ].…”

Section: Determining How Giardia Causes Diseasementioning

confidence: 99%

Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

Bartelt¹,

Sartor²

2015

F1000Prime Rep

126

129

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Giardia lamblia is a flagellated protozoan that is the most common cause of intestinal parasitic infection in children living in resource-limited settings. The pathogenicity of Giardia has been debated since the parasite was first identified, and clinical outcomes vary across studies. Among recent perplexing findings are diametrically opposed associations between Giardia and acute versus persistent diarrhea and a poorly understood potential for long-term sequelae, including impaired child growth and cognitive development. The mechanisms driving these protean clinical outcomes remain elusive, but recent advances suggest that variability in Giardia strains, host nutritional status, the composition of microbiota, co-infecting enteropathogens, host genetically determined mucosal immune responses, and immune modulation by Giardia are all relevant factors influencing disease manifestations after Giardia infection.

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“…Independent of whether adhesion results from a mere mechanical adhesion through the ventral disk or involves ligand–receptor interactions, the host cells are not passive recipients for Giardia attachment but are active participants, having evolved specialized strategies to resist infection. These include, for example, the amplification and regulation of the expression of genes, many of which are involved in the immunological defense of host cells to Giardia ( Ferella et al, 2014 ). The importance of the early transcription of genes coding for components of intestinal mucosal immunity can be appreciated by studies using animal models.…”

Section: Giardia Lamblia and Giardiasismentioning

confidence: 99%

Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses

Genova

Tonelli

2016

Front. Microbiol.

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Giardia lamblia, Cryptosporidium sp., and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading causes worldwide of diarrheal illness in humans. Diseases caused by these organisms, giardiasis, cryptosporidiosis, and amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these three pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite–host interaction and in the mechanisms implicated in the diseases’ pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways, and cell death.

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Gene expression changes during Giardia–host cell interactions in serum-free medium

Cited by 18 publications

References 20 publications

Induction of virulence factors in Giardia duodenalis independent of host attachment

Induction of virulence factors in Giardia duodenalis independent of host attachment

Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses

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