Antigenic variation in the intestinal parasite Giardia lamblia

Gargantini, Pablo Rubén; Serradell, Marianela del Carmen; Ríos, Diego Nicolás; Tenaglia, Albano H.; Luján, Hugo D.

doi:10.1016/j.mib.2016.04.017

Cited by 48 publications

(37 citation statements)

References 42 publications

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“…G. intestinalis is not known to possess classical virulence factors, such as enterotoxins, but several genes are important for colonization of the host and thus for pathogenesis. These include genes for motility [10], the adhesive disc for attachment [9], secreted cysteine proteases that can degrade host defensive factors [12, 13], and cysteine-rich surface protein like the VSPs [52] and the HCMPs [49] that undergo antigenic variation. The cytoskeletal protein repertoire in G. muris is very similar to G. intestinalis apart from several fragmented alpha-tubulins (three complete genes with homologues in G. intestinalis and nine incomplete gene fragments).…”

Section: Resultsmentioning

confidence: 99%

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

Jiménez-González

Einarsson

et al. 2020

Microbial Genomics

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Diplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to G. intestinalis, G. muris maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host–pathogen interaction in the G. muris–mouse pathosystem.

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Section: Resultsmentioning

confidence: 99%

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

Jiménez-González

Einarsson

et al. 2020

Microbial Genomics

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“…Selection of a VSP, rather than switching, has been suggested for VSPH7 of the assemblage B isolate GS-M in the mouse model of infection (21); however, the large number of trophozoites recovered at 4 dpi indicated that VSP switching is more likely to occur than selection of a different VSP in surviving trophozoites. Several stimuli other than antibodies have been proposed to induce antigenic variation (22,23). Thus, it is likely that environmental changes (culture versus intestinal conditions) could trigger VSP switching.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, it is likely that environmental changes (culture versus intestinal conditions) could trigger VSP switching. It is also possible that mechanisms of the innate immune system, such as oxidative stress (reactive nitric and oxygen species) and/or soluble intestinal factors (22,23) might favor this accelerated change in VSP expression over in vitro switching ( Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

Cytokines, Antibodies, and Histopathological Profiles during Giardia Infection and Variant-Specific Surface Protein-Based Vaccination

et al. 2018

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Giardiasis is one of the most common human intestinal diseases worldwide. Several experimental animal models have been used to evaluate infections, with gerbils () being the most valuable model due to their high susceptibility to infection, abundant shedding of cysts, and pathophysiological alterations and signs of disease similar to those observed in humans. Here, we report cytokine and antibody profiles both during the course of infection in gerbils and after immunization with a novel oral vaccine comprising a mixture of purified variant-specific surface proteins (VSPs). Transcript levels of representative cytokines of different immune profiles as well as macro- and microtissue alterations were assessed in Peyer's patches, mesenteric lymph nodes, and spleens. During infection, cytokine responses showed a biphasic profile: an early induction of Th1 (gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-6, and tumor necrosis factor [TNF]), Th17 (IL-17), and Th2 (IL-4) cytokines, together with intestinal alterations typical of inflammation, followed by a shift toward a predominant Th2 (IL-5) response, likely associated with a counterregulatory mechanism. Conversely, immunization with an oral vaccine comprising the entire repertoire of VSPs specifically showed high levels of IL-17, IL-6, IL-4, and IL-5, without obvious signs of inflammation. Both immunized and infected animals developed local (intestinal secretory IgA [S-IgA]) and systemic (serum IgG) humoral immune responses against VSPs; however, only infected animals showed evident signs of giardiasis. This is the first comprehensive report of cytokine expression and anti- antibody production during infection and VSP vaccination in gerbils, a reliable model of the human disease.

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“…15 VSPs belong to a widely varying cysteine-rich group of proteins, and also contribute to host immune evasion through antigenic variation. 16 The antigenic variation of VSPs, occurring by epigenetic mechanisms, may Figure 1. Giardia interactions with gut triple barrier (microbiota, mucus, epithelium).…”

Section: Parasitic and Host Factors During Giardia-host Cell Interactionmentioning

confidence: 99%

Interactions ofGiardia sp.with the intestinal barrier: Epithelium, mucus, and microbiota

et al. 2017

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Understanding how intestinal enteropathogens cause acute and chronic alterations has direct animal and human health perspectives. Significant advances have been made on this field by studies focusing on the dynamic crosstalk between the intestinal protozoan parasite model Giardia duodenalis and the host intestinal mucosa. The concept of intestinal barrier function is of the highest importance in the context of many gastrointestinal diseases such as infectious enteritis, inflammatory bowel disease, and post-infectious gastrointestinal disorders. This crucial function relies on 3 biotic and abiotic components, first the commensal microbiota organized as a biofilm, then an overlaying mucus layer, and finally the tightly structured intestinal epithelium. Herein we review multiple strategies used by Giardia parasite to circumvent these 3 components. We will summarize what is known and discuss preliminary observations suggesting how such enteropathogen directly and/ or indirectly impairs commensal microbiota biofilm architecture, disrupts mucus layer and damages host epithelium physiology and survival.

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Antigenic variation in the intestinal parasite Giardia lamblia

Cited by 48 publications

References 42 publications

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

Cytokines, Antibodies, and Histopathological Profiles during Giardia Infection and Variant-Specific Surface Protein-Based Vaccination

Interactions ofGiardia sp.with the intestinal barrier: Epithelium, mucus, and microbiota

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