{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:54:59Z","timestamp":1767167699692,"version":"build-2238731810"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Entamoeba histolytica<\/jats:named-content>\n                    than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. histolytica<\/jats:named-content>\n                    via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized\n                    <jats:italic>LEPR<\/jats:italic>\n                    Q or R allele at codon 223 were intracecally infected with\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. histolytica<\/jats:named-content>\n                    . Susceptibility to amebiasis was assessed, and cecal tissues were analyzed for changes in gene expression. By 72 h postchallenge, all Q223 mice had cleared\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. histolytica<\/jats:named-content>\n                    , whereas 39% of 223R mice were infected. Thirty-seven genes were differentially expressed in response to infection at 72 h, including proinflammatory genes (\n                    <jats:italic>CXCL2<\/jats:italic>\n                    ,\n                    <jats:italic>S100A8\/9<\/jats:italic>\n                    ,\n                    <jats:italic>PLA2G7<\/jats:italic>\n                    ,\n                    <jats:italic>ITBG2<\/jats:italic>\n                    , and\n                    <jats:italic>MMP9<\/jats:italic>\n                    ) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h postchallenge of infected Q223 versus R223 mice identified a subset of differentially expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. histolytica<\/jats:named-content>\n                    . As such, they are important for the insight that they provide into this previously uncharacterized mechanism of mucosal immunity.\n                  <\/jats:p>","DOI":"10.1128\/iai.01383-12","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T02:15:35Z","timestamp":1361326535000},"page":"1460-1470","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica"],"prefix":"10.1128","volume":"81","author":[{"given":"Nicole M.","family":"Mackey-Lawrence","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoti","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA"},{"name":"North Shore Long Island Health System, Manhasset, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"Sturdevant","sequence":"additional","affiliation":[{"name":"Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimmo","family":"Virtaneva","sequence":"additional","affiliation":[{"name":"Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew M.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Houpt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Sher","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen F.","family":"Porcella","sequence":"additional","affiliation":[{"name":"Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"William A.","family":"Petri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1210\/jcem.84.10.5999","article-title":"Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects","volume":"84","author":"Ozata M","year":"1999","unstructured":"OzataMOzdemirICLicinioJ. 1999. 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