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      Immunological aspects of Giardia infections Translated title: Aspects immunologiques des infections à Giardia

      1 , 2 , *

      Parasite

      EDP Sciences

      Giardia intestinalis, Giardiasis, NO

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          Abstract

          Immunodeficiency, particularly antibody deficiency, predisposes to increased intensity and persistence of Giardia infections. Giardia-infected immunocompetent hosts produce serum and intestinal antibodies against Giardia trophozoites. The number of Giardia muris trophozoites, in mice with G. muris infection, is reduced by intra-duodenal administration of anti- G. muris antibody. Giardia intestinalis antigens that are recognised by human anti-trophozoite antibodies include variable (variant-specific) and invariant proteins. Nitric oxide (NO) appears to contribute to host clearance of Giardia trophozoites. Arginine is a precursor of NO and is metabolised by Giardia trophozoites, possibly reducing its availability for generation of NO by the host. Work with mice suggests that T lymphocytes and interleukin-6 (IL-6) contribute to clearance of Giardia infection via mechanisms independent of antibodies.

          Translated abstract

          L’immunodéficience, particulièrement la déficience en anticorps, prédispose à une augmentation de l’intensité et de la durée des infections à Giardia. Les hôtes immunocompétents infectés par Giardia produisent des anticorps sériques et intestinaux contre les trophozoïtes de Giardia. Le nombre de trophozoïtes de Giardia muris, chez la souris infectée par G. muris, est réduit par l’administration intra-duodénale d’anticorps anti G. muris. Les antigènes de Giardia intestinalis qui sont reconnus par des anticorps humains anti-trophozoïtes comprennent des protéines variables (spécifiques aux variants) et des protéines invariantes. L’oxyde nitrique (NO) semble contribuer à débarrasser l’hôte des trophozoïtes de Giardia. L’arginine est un précurseur de NO et est métabolisé par les trophozoïtes de Giardia, ce qui réduit peut-être sa disponibilité pour la production de NO par l’hôte. Les travaux sur la souris suggèrent que les lymphocytes T et l’interleukine-6 (IL-6) contribuent à éliminer Giardia par des mécanismes indépendants des anticorps.

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          Most cited references 30

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          Mucosal defences against Giardia.

           Lars Eckmann (2003)
          Giardia lamblia (syn. G. duodenalis or G. intestinalis), the causative agent of giardiasis, is one of the most common causes worldwide of intestinal infections in humans. Symptomatic infection is characterized by diarrhoea, epigastric pain, nausea, vomiting, and weight loss, yet many infections are asymptomatic. The protozoan, unicellular parasite resides in the lumen and attaches to the epithelium and overlying mucus layers but does not invade the mucosa and causes little or no mucosal inflammation. Giardiasis is normally transient, indicating the existence of effective host defences, although re-infections can occur, which may be related to differences in infecting parasites and/or incomplete immune protection. Mucosal defences against Giardia must act in the small intestinal lumen in the absence of induction by classical inflammatory mediators. Secretory IgA antibodies have a central role in anti-giardial defence. B cell-independent mechanisms also exist and can contribute to eradication of the parasite, although their identity and physiological importance are poorly understood currently. Possible candidates are nitric oxide, antimicrobial peptides such as Paneth cell alpha-defensins, and lactoferrin. Elucidation of the key anti-giardial effector mechanisms will be important for selecting the best adjuvants in the rational development of vaccination strategies against Giardia.
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            Surface antigenic variation in Giardia lamblia.

             William Nash (2002)
            Giardia lamblia, a common intestinal dwelling protozoan and a cause of diarrhoea in humans and animals world-wide, undergoes surface antigenic variation. The variant-specific surface proteins (VSPs) are a family of related, highly unusual proteins that cover the entire surface of the parasite. VSPs are cysteine-rich proteins containing many CXXC motifs, one or two GGCY motifs, a conserved hydrophobic tail and a Zn finger motif. The biological role(s) of VSPs is unclear. As VSPs are resistant to the effects of intestinal proteases, they likely allow the organism to survive in the protease-rich small intestine. Although immune escape is commonly mentioned as the reason antigenic variation occurs, VSP expression changes in vivo even in the absence of an adaptive immune system suggesting the biological role of antigenic variation is more complex. The molecular mechanisms involved in antigenic variation are not known but appear to differ from those known to occur in other protozoa.
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              Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells

              In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the host´s production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that citrulline especially should gain further attention in future treatment strategies.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2014
                28 October 2014
                : 21
                : ( publisher-idID: parasite/2014/01 )
                Affiliations
                [1 ] Research Service, Department of Veterans Affairs (VA) Medical Center Philadelphia PA 19104 USA
                [2 ] Department of Medicine, Perelman School of Medicine, University of Pennsylvania Philadelphia PA 19104 USA
                Author notes
                [* ]Corresponding author: martin.heyworth@ 123456va.gov
                Article
                parasite140090 10.1051/parasite/2014056
                10.1051/parasite/2014056
                4209855
                25347704
                © M.F. Heyworth, published by EDP Sciences, 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 36, Pages: 4
                Categories
                Review Article

                no, giardiasis, giardia intestinalis

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