{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:35:18Z","timestamp":1786538118952,"version":"build-2736575974"},"reference-count":124,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut Pasteur"},{"name":"Institut Pasteur"},{"name":"Institut Pasteur"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Microorganisms have long been suspected to influence the outcome of immune-related syndromes, particularly autoimmune diseases. Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing beta cells of pancreatic islets, causing high glycemia levels. Genetics is part of its aetiology, but environmental factors, particularly infectious microorganisms, also play a role. Bacteria, viruses, and parasites influence the outcome of T1D in mice and humans. We used nonobese diabetic (NOD) mice, which spontaneously develop T1D, to investigate the influence of a parasitic infection, leishmaniasis. <jats:italic>Leishmania amazonensis<\/jats:italic> is an intracellular eukaryotic parasite that replicates predominantly in macrophages and is responsible for cutaneous leishmaniasis. The implication of Th1 immune responses in T1D and leishmaniasis led us to study this parasite in the NOD mouse model. We previously constructed osteopontin knockout mice with a NOD genetic background and demonstrated that this protein plays a role in the T1D phenotype. In addition, osteopontin (OPN) has been found to play a role in the immune response to various infectious microorganisms and to be implicated in other autoimmune conditions, such as multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in mice. We present herein data demonstrating the role of OPN in the response to <jats:italic>Leishmania<\/jats:italic> in NOD mice and the influence of this parasitic infection on T1D. This exploratory study aimed to investigate the environmental infectious component of the autoimmune response, including Th1 immunity, which is common to both T1D and leishmaniasis.<\/jats:p>","DOI":"10.1371\/journal.pone.0308868","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T17:28:13Z","timestamp":1729618093000},"page":"e0308868","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Type 1 diabetes and parasite infection: An exploratory study in NOD mice"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0028-1944","authenticated-orcid":true,"given":"Emilie","family":"Giraud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Fiette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-4788","authenticated-orcid":true,"given":"Evie","family":"Melanitou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"issue":"1","key":"pone.0308868.ref001","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12016-011-8285-8","article-title":"Hygiene Hypothesis and Autoimmune Diseases","volume":"42","author":"GAW Rook","year":"2012","journal-title":"Clin Rev Allerg Immu"},{"issue":"6710","key":"pone.0308868.ref002","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1136\/bmj.299.6710.1259","article-title":"Hay fever, hygiene, and household size","volume":"299","author":"DP Strachan","year":"1989","journal-title":"BMJ"},{"issue":"10","key":"pone.0308868.ref003","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1038\/ni.3829","article-title":"The immunology of the allergy epidemic and the hygiene hypothesis","volume":"18","author":"BN Lambrecht","year":"2017","journal-title":"Nat Immunol"},{"issue":"2","key":"pone.0308868.ref004","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nri.2017.111","article-title":"The hygiene hypothesis in autoimmunity: the role of pathogens and commensals","volume":"18","author":"JF Bach","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"pone.0308868.ref005","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fimmu.2019.00388","article-title":"The Hygiene Hypothesis, Old Friends, and New Genes","volume":"10","author":"JW Frew","year":"2019","journal-title":"Front Immunol"},{"issue":"2","key":"pone.0308868.ref006","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00592-006-0210-x","article-title":"Negative association between occurrence of type 1 diabetes and tuberculosis incidence at population level","volume":"43","author":"L Airaghi","year":"2006","journal-title":"Acta Diabetol"},{"issue":"2","key":"pone.0308868.ref007","first-page":"a007799","article-title":"The hygiene hypothesis: an explanation for the increased frequency of insulin-dependent diabetes","volume":"2","author":"JF Bach","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"1797","key":"pone.0308868.ref008","article-title":"Running with the Red Queen: the role of biotic conflicts in evolution","volume":"281","author":"MA Brockhurst","year":"2014","journal-title":"Proc Biol Sci"},{"key":"pone.0308868.ref009","doi-asserted-by":"crossref","first-page":"10004","DOI":"10.1038\/srep10004","article-title":"Red Queen dynamics in multi-host and multi-parasite interaction system","volume":"5","author":"JF Rabajante","year":"2015","journal-title":"Sci Rep"},{"issue":"6","key":"pone.0308868.ref010","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.micinf.2010.02.002","article-title":"The hygiene hypothesis: an evolutionary perspective","volume":"12","author":"M Sironi","year":"2010","journal-title":"Microbes Infect"},{"key":"pone.0308868.ref011","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"NH Cho","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"pone.0308868.ref012","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","article-title":"IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040","volume":"128","author":"K Ogurtsova","year":"2017","journal-title":"Diabetes Res Clin Pract"},{"key":"pone.0308868.ref013","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.gde.2018.01.006","article-title":"Genetics of type 1 diabetes","volume":"50","author":"CC Robertson","year":"2018","journal-title":"Curr Opin Genet Dev"},{"issue":"3","key":"pone.0308868.ref014","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/pedi.12597","article-title":"Genetics of type 1 diabetes","volume":"19","author":"MJ Redondo","year":"2018","journal-title":"Pediatr Diabetes"},{"issue":"4","key":"pone.0308868.ref015","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2010.04.001","article-title":"Etiology of type 1 diabetes","volume":"32","author":"JA Todd","year":"2010","journal-title":"Immunity"},{"issue":"Suppl 1","key":"pone.0308868.ref016","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000329169","article-title":"Pathogenesis of type 1 diabetes: implications for incidence trends","volume":"76","author":"M. Knip","year":"2011","journal-title":"Horm Res Paediatr"},{"issue":"4","key":"pone.0308868.ref017","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/ni0411-273","article-title":"Gene-environment interactions in chronic inflammatory disease","volume":"12","author":"H Renz","year":"2011","journal-title":"Nat Immunol"},{"issue":"4","key":"pone.0308868.ref018","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4161\/isl.21570","article-title":"The microbiology of human hygiene and its impact on type 1 diabetes","volume":"4","author":"NM Chapman","year":"2012","journal-title":"Islets"},{"issue":"6","key":"pone.0308868.ref019","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1084\/jem.171.6.2077","article-title":"Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence","volume":"171","author":"MB Oldstone","year":"1990","journal-title":"J Exp Med"},{"issue":"6","key":"pone.0308868.ref020","first-page":"1515","article-title":"Immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice","volume":"119","author":"CM Filippi","year":"2009","journal-title":"J Clin Invest"},{"issue":"11","key":"pone.0308868.ref021","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.2337\/db07-1023","article-title":"Viral Trigger for Type 1 Diabetes Pros and Cons","volume":"57","author":"CM Filippi","year":"2008","journal-title":"Diabetes"},{"key":"pone.0308868.ref022","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.diabet.2008.05.008","article-title":"Role of coxsackievirus B4 in the pathogenesis of type 1 diabetes","volume":"34","author":"H Jaidane","year":"2008","journal-title":"Diabetes Metab"},{"issue":"3","key":"pone.0308868.ref023","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/dmrr.2673","article-title":"Parasitic helminths and their beneficial impact on type 1 and type 2 diabetes","volume":"32","author":"A Berbudi","year":"2016","journal-title":"Diabetes Metab Res Rev"},{"issue":"8","key":"pone.0308868.ref024","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1007\/s00436-017-5544-5","article-title":"Therapeutic potential of helminths in autoimmune diseases: helminth-derived immune-regulators and immune balance","volume":"116","author":"M Wang","year":"2017","journal-title":"Parasitol Res"},{"issue":"6","key":"pone.0308868.ref025","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S2213-8587(16)30081-X","article-title":"The global diabetes epidemic: what does it mean for infectious diseases in tropical countries?","volume":"5","author":"R van Crevel","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"pone.0308868.ref026","first-page":"34","article-title":"TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment","author":"DL Faustman","year":"2018","journal-title":"Diabetes Metab Res Rev"},{"issue":"9","key":"pone.0308868.ref027","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41574-018-0064-7","article-title":"BCG vaccination for type 1 diabetes mellitus","volume":"14","author":"I. Leong","year":"2018","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"pone.0308868.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MRM.0000000000000155","article-title":"The diabetes pandemic and associated infections: suggestions for clinical microbiology","volume":"30","author":"A Toniolo","year":"2019","journal-title":"Rev Med Microbiol"},{"issue":"3","key":"pone.0308868.ref029","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/039463200702000302","article-title":"Immunopathology of leishmaniasis: an update","volume":"20","author":"P Mansueto","year":"2007","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"5","key":"pone.0308868.ref030","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1684\/ejd.2009.0732","article-title":"Unusual multifocal cutaneous leishmaniasis in a diabetic patient","volume":"19","author":"AM Ceyhan","year":"2009","journal-title":"Eur J Dermatol"},{"issue":"12","key":"pone.0308868.ref031","doi-asserted-by":"crossref","first-page":"ofaa491","DOI":"10.1093\/ofid\/ofaa491","article-title":"Diabetes Modifies the Clinic Presentation of Cutaneous Leishmaniasis.","volume":"7","author":"AS Lago","year":"2020","journal-title":"Open Forum Infect Dis"},{"issue":"10","key":"pone.0308868.ref032","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.ijpara.2007.04.003","article-title":"Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies","volume":"37","author":"PA Bates","year":"2007","journal-title":"Int J Parasitol"},{"issue":"6","key":"pone.0308868.ref033","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1371\/journal.ppat.0030091","article-title":"Leishmania manipulation of sand fly feeding behavior results in enhanced transmission.","volume":"3","author":"ME Rogers","year":"2007","journal-title":"PLoS Pathog"},{"key":"pone.0308868.ref034","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s42003-019-0323-8","article-title":"Quantifying Leishmania Metacyclic Promastigotes from Individual Sandfly Bites Reveals the Efficiency of Vector Transmission","volume":"2","author":"E Giraud","year":"2019","journal-title":"Commun Biol"},{"issue":"1","key":"pone.0308868.ref035","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12866-019-1404-z","article-title":"Osteopontin in the host response to Leishmania amazonensis","volume":"19","author":"E Giraud","year":"2019","journal-title":"BMC Microbiol"},{"issue":"5454","key":"pone.0308868.ref036","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1126\/science.287.5454.860","article-title":"Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity","volume":"287","author":"S Ashkar","year":"2000","journal-title":"Science"},{"key":"pone.0308868.ref037","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1755-8794-2-63","article-title":"Early over expression of messenger RNA for multiple genes, including insulin, in the Pancreatic Lymph Nodes of NOD mice is associated with Islet Autoimmunity","volume":"2","author":"B Regnault","year":"2009","journal-title":"BMC Med Genomics"},{"issue":"2","key":"pone.0308868.ref038","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1530\/EJE-15-0791","article-title":"Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile","volume":"174","author":"I Barchetta","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"pone.0308868.ref039","doi-asserted-by":"crossref","first-page":"144785","DOI":"10.1016\/j.gene.2020.144785","article-title":"Investigation of type 1 diabetes in NOD mice knockout for the osteopontin gene","volume":"753","author":"E. Melanitou","year":"2020","journal-title":"Gene"},{"key":"pone.0308868.ref040","article-title":"Expression-based Genome-Wide Association Study Links OPN and IL1-RA with Newly Diagnosed Type 1 Diabetes in Children","author":"X Jia","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"pone.0308868.ref041","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.clim.2005.07.007","article-title":"The autoimmune contrivance: genetics in the mouse model","volume":"117","author":"E. Melanitou","year":"2005","journal-title":"Clin Immunol"},{"issue":"3","key":"pone.0308868.ref042","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1462-5822.2004.00468.x","article-title":"Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice","volume":"7","author":"T Lang","year":"2005","journal-title":"Cell Microbiol"},{"issue":"1","key":"pone.0308868.ref043","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.micinf.2009.09.014","article-title":"Sorting of Leishmania-bearing dendritic cells reveals subtle parasite-induced modulation of host-cell gene expression","volume":"12","author":"H Lecoeur","year":"2010","journal-title":"Microbes Infect"},{"key":"pone.0308868.ref044","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0031182000060960","article-title":"Megasomes as the targets of leucine methyl ester in Leishmania amazonensis amastigotes","volume":"99","author":"JC Antoine","year":"1989","journal-title":"Parasitology"},{"issue":"4","key":"pone.0308868.ref045","doi-asserted-by":"crossref","first-page":"e2154","DOI":"10.1371\/journal.pntd.0002154","article-title":"High content analysis of primary macrophages hosting proliferating Leishmania amastigotes: application to anti-leishmanial drug discovery","volume":"7","author":"N Aulner","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pone.0308868.ref046","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0166-6851(03)00142-7","article-title":"An in vitro system for developmental and genetic studies of Leishmania donovani phosphoglycans","volume":"130","author":"S Goyard","year":"2003","journal-title":"Mol Biochem Parasitol"},{"key":"pone.0308868.ref047","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1242\/jcs.00860","article-title":"Dendritic cells as host cells for the promastigote and amastigote stages of Leishmania amazonensis: the role of opsonins in parasite uptake and dendritic cell maturation","volume":"117","author":"E Prina","year":"2004","journal-title":"J Cell Sci"},{"issue":"8","key":"pone.0308868.ref048","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.4049\/jimmunol.160.8.3861","article-title":"Mouse cell surface antigens: nomenclature and immunophenotyping","volume":"160","author":"L Lai","year":"1998","journal-title":"J Immunol"},{"issue":"1","key":"pone.0308868.ref049","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1074\/jbc.271.1.486","article-title":"Molecular cloning of F4\/80, a murine macrophage-restricted cell surface glycoprotein with homology to the G-protein-linked transmembrane 7 hormone receptor family","volume":"271","author":"AJ McKnight","year":"1996","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0308868.ref050","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1462-5822.2010.01521.x","article-title":"A combined luciferase imaging and reverse transcription polymerase chain reaction assay for the study of Leishmania amastigote burden and correlated mouse tissue transcript fluctuations","volume":"13","author":"E de La Llave","year":"2011","journal-title":"Cell Microbiol"},{"key":"pone.0308868.ref051","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1471-2199-7-3","article-title":"The RIN: an RNA integrity number for assigning integrity values to RNA measurements","volume":"7","author":"A Schroeder","year":"2006","journal-title":"BMC Mol Biol"},{"issue":"2","key":"pone.0308868.ref052","doi-asserted-by":"crossref","first-page":"R19","DOI":"10.1186\/gb-2007-8-2-r19","article-title":"qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data","volume":"8","author":"J Hellemans","year":"2007","journal-title":"Genome Biol"},{"issue":"7","key":"pone.0308868.ref053","first-page":"3","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","author":"J Vandesompele","year":"2002","journal-title":"Genome Biol"},{"issue":"15","key":"pone.0308868.ref054","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets","volume":"64","author":"CL Andersen","year":"2004","journal-title":"Cancer Res"},{"issue":"12","key":"pone.0308868.ref055","doi-asserted-by":"crossref","first-page":"e1980","DOI":"10.1371\/journal.pntd.0001980","article-title":"Distinct transcriptional signatures of bone marrow-derived C57BL\/6 and DBA\/2 dendritic leucocytes hosting live Leishmania amazonensis amastigotes","volume":"6","author":"E Giraud","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"pone.0308868.ref056","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1645\/GE-256R","article-title":"Comparing parasite numbers between samples of hosts","volume":"90","author":"M Neuhauser","year":"2004","journal-title":"J Parasitol"},{"issue":"3","key":"pone.0308868.ref057","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1645\/GE-2177.1","article-title":"The comparison of mean crowding between two groups","volume":"96","author":"M Neuhauser","year":"2010","journal-title":"J Parasitol"},{"issue":"2","key":"pone.0308868.ref058","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1645\/0022-3395(2000)086[0228:QPISOH]2.0.CO;2","article-title":"Quantifying parasites in samples of hosts","volume":"86","author":"L Rozsa","year":"2000","journal-title":"J Parasitol"},{"issue":"2","key":"pone.0308868.ref059","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1645\/GE-281R1","article-title":"Properties of crowding indices and statistical tools to analyze parasite crowding data","volume":"91","author":"J Reiczigel","year":"2005","journal-title":"J Parasitol"},{"key":"pone.0308868.ref060","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0065-2776(08)00806-7","article-title":"Gene-gene interactions in the NOD mouse model of type 1 diabetes","volume":"100","author":"WM Ridgway","year":"2008","journal-title":"Adv Immunol"},{"issue":"4","key":"pone.0308868.ref061","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1097\/MPA.0000000000000828","article-title":"Development of the Nonobese Diabetic Mouse and Contribution of Animal Models for Understanding Type 1 Diabetes","volume":"46","author":"Y. Mullen","year":"2017","journal-title":"Pancreas"},{"issue":"5214","key":"pone.0308868.ref062","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1126\/science.7761837","article-title":"T helper cell subsets in insulin-dependent diabetes","volume":"268","author":"JD Katz","year":"1995","journal-title":"Science"},{"issue":"8","key":"pone.0308868.ref063","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S1471-4922(02)02352-8","article-title":"Interaction of Leishmania with the host macrophage","volume":"18","author":"E Handman","year":"2002","journal-title":"Trends Parasitol"},{"key":"pone.0308868.ref064","first-page":"83","article-title":"The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response","volume":"2","author":"D Liu","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"issue":"12","key":"pone.0308868.ref065","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1086\/652870","article-title":"Immunopathological studies of Leishmania amazonensis infection in resistant and in susceptible mice","volume":"201","author":"F de Oliveira Cardoso","year":"2010","journal-title":"J Infect Dis"},{"issue":"4","key":"pone.0308868.ref066","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1128\/IAI.73.4.1907-1916.2005","article-title":"Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells","volume":"73","author":"SL Fink","year":"2005","journal-title":"Infect Immun"},{"issue":"5","key":"pone.0308868.ref067","doi-asserted-by":"crossref","first-page":"E801","DOI":"10.1073\/pnas.1619265114","article-title":"Continual renewal and replication of persistent Leishmania major parasites in concomitantly immune hosts","volume":"114","author":"MA Mandell","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pone.0308868.ref068","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0011-5029(97)90028-6","article-title":"Nitric oxide and shock","volume":"43","author":"RG Kilbourn","year":"1997","journal-title":"Dis Mon"},{"issue":"16","key":"pone.0308868.ref069","doi-asserted-by":"crossref","first-page":"8841","DOI":"10.1073\/pnas.97.16.8841","article-title":"Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens","volume":"97","author":"C Nathan","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0308868.ref070","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1369-5274(99)00048-X","article-title":"Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria","volume":"3","author":"MU Shiloh","year":"2000","journal-title":"Curr Opin Microbiol"},{"issue":"1","key":"pone.0308868.ref071","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1186\/s13071-017-2401-4","article-title":"Moroccan strains of Leishmania major and Leishmania tropica differentially impact on nitric oxide production by macrophages","volume":"10","author":"H Maksouri","year":"2017","journal-title":"Parasit Vectors"},{"issue":"12","key":"pone.0308868.ref072","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1016\/j.immuni.2021.09.021","article-title":"Nitric oxide controls proliferation of Leishmania major by inhibiting the recruitment of permissive host cells","volume":"54","author":"P Formaglio","year":"2021","journal-title":"Immunity"},{"issue":"4","key":"pone.0308868.ref073","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1128\/iai.62.4.1478-1479.1994","article-title":"Expression of inducible nitric oxide synthase by stimulated macrophages correlates with their antihistoplasma activity","volume":"62","author":"TE Lane","year":"1994","journal-title":"Infect Immun"},{"issue":"12","key":"pone.0308868.ref074","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.4049\/jimmunol.143.12.4208","article-title":"Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates","volume":"143","author":"SL James","year":"1989","journal-title":"J Immunol"},{"issue":"12","key":"pone.0308868.ref075","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.4049\/jimmunol.144.12.4794","article-title":"Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine","volume":"144","author":"FY Liew","year":"1990","journal-title":"J Immunol"},{"issue":"2","key":"pone.0308868.ref076","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.surg.2008.03.007","article-title":"Osteopontin mediates Stat1 degradation to inhibit iNOS transcription in a cecal ligation and puncture model of sepsis","volume":"144","author":"H Guo","year":"2008","journal-title":"Surgery"},{"issue":"11","key":"pone.0308868.ref077","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1128\/iai.63.11.4495-4500.1995","article-title":"Attenuation of gamma interferon-induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani: selective inhibition of signaling through Janus kinases and Stat1","volume":"63","author":"D Nandan","year":"1995","journal-title":"Infect Immun"},{"issue":"1","key":"pone.0308868.ref078","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijpara.2004.10.018","article-title":"Leishmania inhibits STAT1-mediated IFN-gamma signaling in macrophages: increased tyrosine phosphorylation of dominant negative STAT1beta by Leishmania mexicana","volume":"35","author":"N Bhardwaj","year":"2005","journal-title":"Int J Parasitol"},{"key":"pone.0308868.ref079","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12858-014-0028-z","article-title":"DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers","volume":"15","author":"T Riebeling","year":"2014","journal-title":"BMC Biochem"},{"issue":"9","key":"pone.0308868.ref080","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1038\/jid.2014.121","article-title":"Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal activity of macrophages","volume":"134","author":"A Mahnke","year":"2014","journal-title":"J Invest Dermatol"},{"issue":"5","key":"pone.0308868.ref081","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.chom.2020.03.011","article-title":"Th1-Th2 Cross-Regulation Controls Early Leishmania Infection in the Skin by Modulating the Size of the Permissive Monocytic Host Cell Reservoir","volume":"27","author":"MB Carneiro","year":"2020","journal-title":"Cell Host Microbe"},{"issue":"15","key":"pone.0308868.ref082","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1096\/fasebj.7.15.8262332","article-title":"Osteopontin: a protein with diverse functions","volume":"7","author":"DT Denhardt","year":"1993","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"10","key":"pone.0308868.ref083","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.4049\/jimmunol.170.10.5152","article-title":"The relative contribution of IL-4 receptor signaling and IL-10 to susceptibility to Leishmania major","volume":"170","author":"N Noben-Trauth","year":"2003","journal-title":"J Immunol"},{"issue":"5251","key":"pone.0308868.ref084","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1126\/science.271.5251.987","article-title":"Susceptibility to Leishmania major infection in interleukin-4-deficient mice","volume":"271","author":"N Noben-Trauth","year":"1996","journal-title":"Science"},{"issue":"5","key":"pone.0308868.ref085","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.4049\/jimmunol.0713598","article-title":"IL-17 promotes progression of cutaneous leishmaniasis in susceptible mice","volume":"182","author":"S Lopez Kostka","year":"2009","journal-title":"J Immunol"},{"issue":"1\u20132","key":"pone.0308868.ref086","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.cyto.2006.04.006","article-title":"IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice","volume":"34","author":"G Rajagopalan","year":"2006","journal-title":"Cytokine"},{"issue":"26","key":"pone.0308868.ref087","doi-asserted-by":"crossref","first-page":"15137","DOI":"10.1073\/pnas.261570598","article-title":"T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells","volume":"98","author":"AA Lighvani","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pone.0308868.ref088","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/ar290","article-title":"The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1\/Th2 paradigm in autoimmunity","volume":"3","author":"AN Theofilopoulos","year":"2001","journal-title":"Arthritis Res"},{"issue":"5","key":"pone.0308868.ref089","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1089\/107999003321829971","article-title":"IFN-gamma induction of osteopontin expression in human monocytoid cells","volume":"23","author":"X Li","year":"2003","journal-title":"J Interferon Cytokine Res"},{"issue":"1","key":"pone.0308868.ref090","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1590\/S0074-02762007000100013","article-title":"Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl\/6 mice","volume":"102","author":"RO Pinheiro","year":"2007","journal-title":"Memorias do Instituto Oswaldo Cruz"},{"issue":"12","key":"pone.0308868.ref091","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.2337\/diabetes.49.12.2007","article-title":"Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice","volume":"49","author":"DV Serreze","year":"2000","journal-title":"Diabetes"},{"issue":"1","key":"pone.0308868.ref092","doi-asserted-by":"crossref","first-page":"8295","DOI":"10.1038\/s41598-018-26471-9","article-title":"Interferon-gamma drives programmed death-ligand 1 expression on islet beta cells to limit T cell function during autoimmune diabetes","volume":"8","author":"KC Osum","year":"2018","journal-title":"Sci Rep"},{"issue":"12","key":"pone.0308868.ref093","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1007\/BF03402053","article-title":"Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing","volume":"6","author":"H Kampfer","year":"2000","journal-title":"Mol Med"},{"issue":"2","key":"pone.0308868.ref094","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1128\/iai.50.2.588-591.1985","article-title":"Genetic control of systemic Leishmania major infections: dissociation of intrahepatic amastigote replication from control by the Lsh gene","volume":"50","author":"BA Mock","year":"1985","journal-title":"Infect Immun"},{"issue":"5","key":"pone.0308868.ref095","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1128\/iai.56.5.1128-1134.1988","article-title":"Differences in Lsh gene control over systemic Leishmania major and Leishmania donovani or Leishmania mexicana mexicana infections are caused by differential targeting to infiltrating and resident liver macrophage populations","volume":"56","author":"EV Davies","year":"1988","journal-title":"Infect Immun"},{"issue":"3","key":"pone.0308868.ref096","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1084\/jem.152.3.594","article-title":"Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica","volume":"152","author":"JG Howard","year":"1980","journal-title":"J Exp Med"},{"key":"pone.0308868.ref097","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/icb.1981.48","article-title":"Resistance to cutaneous leishmaniasis in genetically susceptible BALB\/c mice","volume":"59","author":"GF Mitchell","year":"1981","journal-title":"Aust J Exp Biol Med Sci"},{"issue":"3","key":"pone.0308868.ref098","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1128\/iai.57.3.875-881.1989","article-title":"Influence of Lsh, H-2, and an H-11-linked gene on visceralization and metastasis associated with Leishmania mexicana infection in mice","volume":"57","author":"M Roberts","year":"1989","journal-title":"Infect Immun"},{"issue":"4","key":"pone.0308868.ref099","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.2337\/db07-1331","article-title":"HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families","volume":"57","author":"H Erlich","year":"2008","journal-title":"Diabetes"},{"issue":"7","key":"pone.0308868.ref100","doi-asserted-by":"crossref","first-page":"e2282","DOI":"10.1371\/journal.pntd.0002282","article-title":"Mapping the genes for susceptibility and response to Leishmania tropica in mouse","volume":"7","author":"Y Sohrabi","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"pone.0308868.ref101","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3389\/fimmu.2019.01083","article-title":"Novel Loci Controlling Parasite Load in Organs of Mice Infected With Leishmania major, Their Interactions and Sex Influence","volume":"10","author":"T Kobets","year":"2019","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0308868.ref102","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S1074-7613(00)80343-X","article-title":"Serial backcross mapping of multiple loci associated with resistance to Leishmania major in mice","volume":"6","author":"AM Beebe","year":"1997","journal-title":"Immunity"},{"issue":"3","key":"pone.0308868.ref103","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jaut.2005.08.010","article-title":"Immunopathogenic role of TH1 cells in autoimmune diabetes: evidence from a T1 and T2 doubly transgenic non-obese diabetic mouse model","volume":"25","author":"JT Hung","year":"2005","journal-title":"J Autoimmun"},{"key":"pone.0308868.ref104","doi-asserted-by":"crossref","first-page":"7675437","DOI":"10.1155\/2016\/7675437","article-title":"Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases","volume":"2016","author":"N Clemente","year":"2016","journal-title":"J Immunol Res"},{"issue":"2","key":"pone.0308868.ref105","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.cyto.2012.10.027","article-title":"Osteopontin-dependent regulation of Th1 and Th17 cytokine responses in Trypanosoma cruzi-infected C57BL\/6 mice","volume":"61","author":"MH Santamaria","year":"2013","journal-title":"Cytokine"},{"issue":"1","key":"pone.0308868.ref106","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/jid.2014.305","article-title":"Genomic profiling of human Leishmania braziliensis lesions identifies transcriptional modules associated with cutaneous immunopathology","volume":"135","author":"FO Novais","year":"2015","journal-title":"J Invest Dermatol"},{"issue":"9","key":"pone.0308868.ref107","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1182\/blood-2012-06-436212","article-title":"Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences","volume":"121","author":"FO Martinez","year":"2013","journal-title":"Blood"},{"issue":"3","key":"pone.0308868.ref108","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1086\/653829","article-title":"T-bet, GATA-3, and Foxp3 expression and Th1\/Th2 cytokine production in the clinical outcome of human infection with Leishmania (Viannia) species","volume":"202","author":"YR Diaz","year":"2010","journal-title":"J Infect Dis"},{"issue":"6","key":"pone.0308868.ref109","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.2337\/db08-1113","article-title":"Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice","volume":"58","author":"JA Emamaullee","year":"2009","journal-title":"Diabetes"},{"issue":"1","key":"pone.0308868.ref110","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1084\/jem.20071878","article-title":"Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production","volume":"205","author":"R Jain","year":"2008","journal-title":"J Exp Med"},{"key":"pone.0308868.ref111","doi-asserted-by":"crossref","first-page":"718946","DOI":"10.1155\/2014\/718946","article-title":"Serum IL-17, IL-23, and TGF-beta levels in type 1 and type 2 diabetic patients and age-matched healthy controls","volume":"2014","author":"A Roohi","year":"2014","journal-title":"Biomed Res Int"},{"key":"pone.0308868.ref112","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.19.1.683","article-title":"Interleukin-10 and the interleukin-10 receptor","volume":"19","author":"KW Moore","year":"2001","journal-title":"Annu Rev Immunol"},{"key":"pone.0308868.ref113","doi-asserted-by":"crossref","first-page":"702955","DOI":"10.3389\/fimmu.2021.702955","article-title":"IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice","volume":"12","author":"J Huang","year":"2021","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0308868.ref114","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.4049\/jimmunol.158.5.2259","article-title":"Both innate and acquired immunity to Listeria monocytogenes infection are increased in IL-10-deficient mice","volume":"158","author":"WJ Dai","year":"1997","journal-title":"J Immunol"},{"issue":"9","key":"pone.0308868.ref115","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1128\/IAI.71.9.4850-4856.2003","article-title":"Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10-deficient mice are ameliorated by anti-tumor necrosis factor alpha and exacerbated by anti-transforming growth factor beta antibodies","volume":"71","author":"C Li","year":"2003","journal-title":"Infect Immun"},{"issue":"7","key":"pone.0308868.ref116","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.4049\/jimmunol.161.7.3299","article-title":"IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice","volume":"161","author":"E Bettelli","year":"1998","journal-title":"J Immunol"},{"issue":"2","key":"pone.0308868.ref117","doi-asserted-by":"crossref","first-page":"828","DOI":"10.4049\/jimmunol.173.2.828","article-title":"IL-10 plays an important role in the homeostatic regulation of the autoreactive repertoire in naive mice","volume":"173","author":"AC Anderson","year":"2004","journal-title":"J Immunol"},{"key":"pone.0308868.ref118","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.iy.13.040195.001055","article-title":"The regulation of immunity to Leishmania major","volume":"13","author":"SL Reiner","year":"1995","journal-title":"Annu Rev Immunol"},{"issue":"11","key":"pone.0308868.ref119","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/ni725","article-title":"IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB\/c mice","volume":"2","author":"T Biedermann","year":"2001","journal-title":"Nat Immunol"},{"issue":"2","key":"pone.0308868.ref120","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0369-8114(03)00101-9","article-title":"The use of the murine model of infection with Leishmania major to reveal the antagonistic effects that IL-4 can exert on T helper cell development and demonstrate that these opposite effects depend upon the nature of the cells targeted for IL-4 signaling","volume":"51","author":"JA Louis","year":"2003","journal-title":"Pathol Biol (Paris)"},{"issue":"2","key":"pone.0308868.ref121","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.4049\/jimmunol.166.2.1079","article-title":"Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages","volume":"166","author":"H Guo","year":"2001","journal-title":"J Immunol"},{"issue":"2","key":"pone.0308868.ref122","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S0962-8924(00)01900-0","article-title":"Nitric oxide and the regulation of gene 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