{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:09:14Z","timestamp":1788880154357,"version":"build-2803163510"},"reference-count":39,"publisher":"American Society of Tropical Medicine and Hygiene","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    The demographics of leishmaniasis in Brazil have shifted in recent decades, coinciding with dietary changes and an increase in overweight\/obesity. Cutaneous leishmaniasis becomes more treatment refractory in obese individuals, highlighting the impact of obesity on disease outcome. The impact of the overweight\/obese state on infection with\n                    <jats:italic>Leishmania infantum<\/jats:italic>\n                    , which causes visceral leishmaniasis (VL), is unclear. We previously showed that an obesity-prone diet restricts\n                    <jats:italic>L. infantum<\/jats:italic>\n                    expansion in the livers of mice, but the immunological basis remained unexplored. Herein, we investigated whether this reflected improved granuloma formation and parasite control or a response to diet-induced hepatic steatosis and inflammation. To evaluate hepatic responses to VL during obesity, mice were maintained on a high-fat, high-cholesterol (HFHC) diet or a control diet before and throughout\n                    <jats:italic>L. infantum<\/jats:italic>\n                    infection. High-fat, high-cholesterol feeding significantly reduced hepatic parasite burdens but increased splenic parasite burdens. Control animals developed well-organized hepatic granulomas before local resolution, whereas HFHC-fed mouse livers developed diffuse inflammation and early fibrosis consistent with steatohepatitis. They completely failed to form mature granulomas. Quantitative analysis confirmed organized granulomas in 100% of infected control mice, whereas HFHC-fed infected mice showed no or else loosely aggregated, immature infiltrates in their livers. Transcriptional profiling revealed a pronounced inflammatory response in na\u00efve HFHC-fed livers that was minimally exacerbated by infection. These data suggest that diet-induced obesity does not prevent an inflammatory response to the parasite. Rather, the obesity diet impairs formation of the tissue-specific granulomatous response that might normally contain\n                    <jats:italic>L. infantum<\/jats:italic>\n                    locally in the liver.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.26-0170","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:37:30Z","timestamp":1788878250000},"source":"Crossref","is-referenced-by-count":0,"title":["Obesity-Associated Inflammatory Reprogramming Impairs a Granulomatous Response to Leishmania infantum"],"prefix":"10.4269","author":[{"given":"Natalie C.","family":"Jarvis","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace M.","family":"Gutzman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yani","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA;"},{"name":"Veterans\u2019 Affairs Medical Center, Iowa City, Iowa, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayan","family":"Zhanbolat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA;"},{"name":"Veterans\u2019 Affairs Medical Center, Iowa City, Iowa, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen I.","family":"Cyndari","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Iowa, Iowa City, Iowa, USA;"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA;"},{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA;"},{"name":"Veterans\u2019 Affairs Medical Center, Iowa City, Iowa, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"issue":"10151","key":"b1","series-title":"Lancet","first-page":"951","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018"},{"issue":"4","key":"b2","series-title":"Microb Pathog","first-page":"147","article-title":"Immunopathogenesis of infection with the visceralizing Leishmania species","volume":"38","author":"Wilson","year":"2005"},{"issue":"12","key":"b3","series-title":"Clin Infect Dis","first-page":"2036","article-title":"Asymptomatic visceral Leishmania infantum infection in US soldiers deployed to Iraq","volume":"68","author":"Mody","year":"2019"},{"issue":"11","key":"b4","series-title":"Clin Infect Dis","first-page":"1674","article-title":"Old World leishmaniasis: An emerging infection among deployed US military and civilian workers","volume":"39","author":"Weina","year":"2004"},{"issue":"10","key":"b5","series-title":"Microbiol Spectr","first-page":"e0105524","article-title":"Descriptive and molecular epidemiology of leishmaniasis diagnosed from clinical samples in the United States, 2021\u20132022","volume":"12","author":"Truong","year":"2024"},{"issue":"3","key":"b6","series-title":"Diagnostics (Basel)","first-page":"670","article-title":"Diagnosis of visceral leishmaniasis in an elimination setting: A validation study of the diagnostic algorithm in India","volume":"12","author":"Cloots","year":"2022"},{"issue":"1","key":"b7","series-title":"Infect Dis Clin North Am","first-page":"101","article-title":"Cutaneous leishmaniasis: Updates in diagnosis and management","volume":"33","author":"Aronson","year":"2019"},{"issue":"12","key":"b8","series-title":"Nutrients","first-page":"2472","article-title":"Food and nutrition public policies in Brazil: From malnutrition to obesity","volume":"14","author":"Moriguchi Watanabe","year":"2022"},{"issue":"1","key":"b9","series-title":"Obes Facts","first-page":"19","article-title":"Malnutrition in obesity: Is it possible?","volume":"15","author":"Kobyli\u0144ska","year":"2022"},{"issue":"2","key":"b10","series-title":"Proc Nutr Soc","first-page":"298","article-title":"The impact of obesity on the immune response to infection","volume":"71","author":"Milner","year":"2012"},{"issue":"6","key":"b11","series-title":"Clin Infect Dis","first-page":"1020","article-title":"Influence of obesity on clinical manifestations and response to therapy in cutaneous leishmaniasis caused by Leishmania braziliensis.","volume":"73","author":"Lago","year":"2021"},{"issue":"6","key":"b12","series-title":"Int J Mol Sci","first-page":"1296","article-title":"Cutaneous manifestations of human and murine leishmaniasis","volume":"18","author":"Scorza","year":"2017"},{"key":"b13","series-title":"Front Immunol","first-page":"251","article-title":"Immunobiology of visceral leishmaniasis","volume":"3","author":"Kumar","year":"2012"},{"issue":"12","key":"b14","series-title":"Parasitology","first-page":"1647","article-title":"Diet-induced obesity promotes systemic inflammation and increased susceptibility to murine visceral leishmaniasis","volume":"143","author":"Sarn\u00e1glia","year":"2016"},{"issue":"4","key":"b15","series-title":"mSphere","first-page":"e0042321","article-title":"The inflammatory effects of dietary lipids regulate growth of parasites during visceral leishmaniasis","volume":"6","author":"Kiser","year":"2021"},{"issue":"6","key":"b16","series-title":"J Immunol","first-page":"2231","article-title":"Local suppression of IFN-gamma in hepatic granulomas correlates with tissue-specific replication of Leishmania chagasi.","volume":"156","author":"Wilson","year":"1996"},{"issue":"12","key":"b17","series-title":"J Immunol","first-page":"4244","article-title":"Experimental visceral leishmaniasis: Role of endogenous IFN-gamma in host defense and tissue granulomatous response","volume":"143","author":"Squires","year":"1989"},{"issue":"1","key":"b18","series-title":"Exp Parasitol","first-page":"129","article-title":"Leishmania chagasi: Homogenous metacyclic promastigotes isolated by buoyant density are highly virulent in a mouse model","volume":"118","author":"Yao","year":"2008"},{"issue":"11","key":"b19","series-title":"J. Clin. Microbiol","first-page":"3892","article-title":"Serial quantitative PCR assay for detection, species-discrimination and quantification of Leishmania spp. in human samples","volume":"49","author":"Weirather","year":"2011"},{"issue":"8","key":"b20","series-title":"J Antimicrob Chemother","first-page":"1751","article-title":"Study of parasite kinetics with antileishmanial drugs using real-time quantitative PCR in Indian visceral leishmaniasis","volume":"66","author":"Sudarshan","year":"2011"},{"issue":"2","key":"b21","series-title":"Clin Exp Med","first-page":"273","article-title":"Liver biopsy for assessment of chronic liver diseases: A synopsis","volume":"23","author":"Chowdhury","year":"2023"},{"issue":"39","key":"b22","series-title":"World J Gastroenterol","first-page":"11077","article-title":"Liver fibrosis in non-alcoholic fatty liver disease\u2014Diagnostic challenge with prognostic significance","volume":"21","author":"St\u00e5l","year":"2015"},{"key":"b23","series-title":"Front Genet","first-page":"1327984","article-title":"A comparative analysis of RNA-Seq and NanoString technologies in deciphering viral infection response in upper airway lung organoids","volume":"15","author":"Rezapour","year":"2024"},{"issue":"4","key":"b24","series-title":"Bioinformatics","first-page":"523","article-title":"Causal analysis approaches in Ingenuity Pathway Analysis","volume":"30","author":"Kr\u00e4mer","year":"2014"},{"issue":"12","key":"b25","series-title":"Eur J Immunol","first-page":"3556","article-title":"The TGF-b response to Leishmania chagasi in the absence of IL-12","volume":"32","author":"Wilson","year":"2002"},{"issue":"1","key":"b26","series-title":"Nat Commun","first-page":"3125","article-title":"Kupffer cell and recruited macrophage heterogeneity orchestrate granuloma maturation and hepatic immunity in visceral leishmaniasis","volume":"16","author":"Pessenda","year":"2025"},{"key":"b27","series-title":"Immunol Rev","first-page":"239","article-title":"The immunopathology of experimental visceral leishmaniasis","volume":"201","author":"Kaye","year":"2004"},{"key":"b28","series-title":"Inflammation: Basic Principles and Clinical Correlates","first-page":"977","author":"Murray","year":"1999"},{"key":"b29","series-title":"J Clin Tuberc Other Mycobact Dis","first-page":"1","article-title":"Histopathologic review of granulomatous inflammation","volume":"7","author":"Shah","year":"2017"},{"issue":"8","key":"b30","series-title":"Nutrients","first-page":"1330","article-title":"Nutrition and gut microbiota\u2013immune system interplay in chronic diseases","volume":"17","author":"Reis","year":"2025"},{"issue":"9","key":"b31","series-title":"Eur J Clin Nutr","first-page":"1309","article-title":"Nutrition and immunity: Lessons for COVID-19","volume":"75","author":"Calder","year":"2021"},{"key":"b32","series-title":"J. Immunol","first-page":"1858","article-title":"Acquired resistance and granuloma formation in experimental visceral leishmaniasis","volume":"148","author":"Murray","year":"1992"},{"issue":"1","key":"b33","series-title":"Immun Inflamm Dis","first-page":"59","article-title":"Inflammation initiates a vicious cycle between obesity and nonalcoholic fatty liver disease","volume":"9","author":"Luo","year":"2021"},{"issue":"2","key":"b34","series-title":"PLoS One","first-page":"e56100","article-title":"Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis","volume":"8","author":"Dixon","year":"2013"},{"issue":"1","key":"b35","series-title":"Nutr Metab (Lond)","first-page":"28","article-title":"A high-trans fat, high-carbohydrate, high-cholesterol, high-cholate diet-induced nonalcoholic steatohepatitis mouse model and its hepatic immune response","volume":"20","author":"Zhang","year":"2023"},{"issue":"7","key":"b36","series-title":"J Cell Biochem","first-page":"11867","article-title":"Inhibition of TREM-1 attenuates inflammation and lipid accumulation in diet-induced nonalcoholic fatty liver disease","volume":"120","author":"Rao","year":"2019"},{"issue":"2","key":"b37","series-title":"Microbiol Spectr","first-page":"e0067922","article-title":"Tissue specific dual RNA-seq defines host-parasite interplay in murine visceral leishmaniasis caused by Leishmania donovani and Leishmania infantum.","volume":"10","author":"Forrester","year":"2022"},{"key":"b38","series-title":"Rev Inst Med Trop Sao Paulo","first-page":"e92","article-title":"Asymptomatic Leishmania infection in blood donors from a major blood bank in Northeastern Brazil: A cross-sectional study","volume":"62","author":"Silva","year":"2020"},{"issue":"1","key":"b39","series-title":"Parasit Vectors","first-page":"5","article-title":"Identification of asymptomatic Leishmania infections: A scoping review","volume":"15","author":"Ibarra-Meneses","year":"2022"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/aop\/article-10.4269-ajtmh.26-0170\/article-10.4269-ajtmh.26-0170.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/aop\/article-10.4269-ajtmh.26-0170\/article-10.4269-ajtmh.26-0170.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:37:30Z","timestamp":1788878250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/aop\/article-10.4269-ajtmh.26-0170\/article-10.4269-ajtmh.26-0170.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":39,"URL":"https:\/\/doi.org\/10.4269\/ajtmh.26-0170","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}