{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:29:54Z","timestamp":1793316594733,"version":"4.5.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T00:00:00Z","timestamp":1418688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,12,31]],"date-time":"2014-12-31T00:00:00Z","timestamp":1419984000000},"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":["mBio"],"published-print":{"date-parts":[[2014,12,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Amebiasis is an enteric infection caused by\n                    <jats:named-content content-type=\"genus-species\">Entamoeba histolytica<\/jats:named-content>\n                    , with symptoms ranging in severity from asymptomatic colonization to dysentery. Humans with the Q223R leptin receptor mutation have increased susceptibility to amebiasis, but the mechanism has been unclear. Using a mouse model expressing the mutation, we tested the impact of the Q223R mutation on the innate immune response to\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    infection. The 223R mutation resulted in delayed clearance of amebae from the cecum, as had been previously observed. We found that neutrophil influx to the site of the infection was reduced 12\u00a0h after infection in 223R mice. Depletion of neutrophils with anti-Ly6G monoclonal antibody increased susceptibility of wild-type mice to infection, supporting the importance of neutrophils in innate defense. Leptin expression was increased in the cecum by\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    infection, suggesting that leptin could serve as a homing signal for neutrophils to the gut. Interestingly, neutrophils from mice with the 223R mutation had diminished chemotaxis toward leptin. This impaired chemotaxis likely explained the reduced gut infiltration of neutrophils. The newly recognized effect of the leptin receptor Q223R mutation on neutrophil chemotaxis and the impact of this mutation on multiple infectious diseases suggest a broader impact of this mutation on susceptibility to disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The Q223R leptin receptor mutation results in increased susceptibility of children and adults to\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    , one of the leading causes of diarrhea morbidity and mortality in children of the developing world. Here we show that the mutation results in reduced neutrophil infiltration to the site of infection. This decreased infiltration is likely due to the mutation\u2019s impact on neutrophil chemotaxis toward leptin, an inflammatory agent upregulated in the cecum after infection. The significance of this work thus extends beyond understanding\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    susceptibility by also providing insight into the potential impact of leptin on neutrophil function in other states of altered leptin signaling, which include both malnutrition and obesity.\n                  <\/jats:p>","DOI":"10.1128\/mbio.02046-14","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T21:36:03Z","timestamp":1418765763000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during Entamoeba histolytica Infection"],"prefix":"10.1128","volume":"5","author":[{"given":"Caitlin","family":"Naylor","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Burgess","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat","family":"Madan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Buonomo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Razzaq","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Ralston","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"William A.","family":"Petri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022710"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit507"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2010.03.005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45294.of"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094843"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.06140-11"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802142"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0431rev"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2009.00242.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/568343"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01383-12"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.8.4496"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13242"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc10467"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1010539513497218"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.4522"},{"key":"e_1_3_2_18_2","first-page":"270","article-title":"Human neutrophils activated by interferon-y and tumour necrosis factor-\u03b1 kill Entamoeba histolytica trophozoites","volume":"274","author":"Chadee K","year":"1989","unstructured":"ChadeeK . 1989. 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