Cryptosporidium parvum scavenges LDL‐derived cholesterol and micellar cholesterol internalized into enterocytes. (28th January 2013)

• Record Type: Journal Article
• Authors: Ehrenman, Karen; Wanyiri, Jane W.; Bhat, Najma; Ward, Honorine D.; Coppens, Isabelle
• Is Part Of: Cellular microbiology. Volume 15:Number 7(2013:Jul.)
• Page Start: 1182
• Page End: 1197
• Publication Date: 2013-01-28
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12107
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>Cryptosporidium</italic> spp. are responsible for devastating diarrhoea in immunodeficient individuals. In the intestinal tract, the developmental stages of the parasite are confined to the apical surfaces of epithelial cells. Upon invasion, <italic>Cryptosporidium</italic> incorporates the microvillous membrane of the enterocyte to form the parasitophorous vacuole (PV) and sequesters itself from the host cytoplasm by rearranging the host cytoskeleton. <italic>Cryptosporidium parvum</italic> has minimal anabolic capabilities and relies on transporters and salvage pathways to meet its basic metabolic requirements. The cholesterol salvage pathway is crucial for the development of protozoan parasites. In this study, we have examined the sources of cholesterol from <italic>C. parvum</italic> infecting enterocytes. We illustrated that the intracellular stages of <italic>Cryptosporidium</italic> as well as the oocysts shed by the host, contain cholesterol. Incubation of infected enterocytes in lipoprotein‐free medium impairs parasite development and results in substantial decrease in cholesterol content associated with the PV. Among lipoproteins, LDL constitutes an important source of cholesterol for <italic>Cryptosporidium</italic>. Dietary cholesterol incorporated into micelles is internalized into enterocytes by the NPC1L1 transporter. We showed that <italic>C. parvum</italic> also obtains cholesterol from micelles in enterocytes.Pharmacological blockade of NPC1L1 function by ezetimibe or moderate downregulation of NPC1L1 expression decreases parasite infectivity. These observations indicate that, despite its dual sequestration from the intestinal lumen and the host cytoplasm, <italic>C. parvum</italic> can, in fact, obtain cholesterol both from the gut's lumen and the host cell. This study highlights the evolutionary advantages for epicellular pathogens to access to nutrients from the outside and inside of the host cell.</p> </abstract>