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Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop<jats:sc>l<\/jats:sc>-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of<jats:sc>l<\/jats:sc>-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>Nissle and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella enterica<\/jats:named-content>serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with<jats:sc>l<\/jats:sc>-arginine or<jats:sc>l<\/jats:sc>-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with<jats:sc>l<\/jats:sc>-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing<jats:sc>l<\/jats:sc>-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans.<\/jats:p>","DOI":"10.1128\/iai.00380-13","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T02:54:23Z","timestamp":1369104863000},"page":"3515-3526","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":69,"title":["Malaria-Associated<scp>l<\/scp>-Arginine Deficiency Induces Mast Cell-Associated Disruption to Intestinal Barrier Defenses against Nontyphoidal Salmonella Bacteremia"],"prefix":"10.1128","volume":"81","author":[{"given":"Jennifer Y.","family":"Chau","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin M.","family":"Tiffany","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Nimishakavi","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco and Veterans Affairs Medical Center, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazzy","family":"Pakpour","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P.","family":"Mooney","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen L.","family":"Lokken","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George H.","family":"Caughey","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco and Veterans Affairs Medical Center, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee M.","family":"Tsolis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Luckhart","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"World malaria report 2011","author":"WHO","year":"2011","unstructured":"WHO. 2011. 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