{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:28:41Z","timestamp":1790724521172,"version":"4.1.0"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Megacolon is one of the main late complications of Chagas disease, affecting approximately 10% of symptomatic patients. However, studies are needed to understand the mechanisms involved in the progression of this condition. During infection by <jats:italic>Trypanosoma cruzi<\/jats:italic> (<jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic>), an inflammatory profile sets in that is involved in neural death, and this destruction is known to be essential for megacolon progression. One of the proteins related to the maintenance of intestinal neurons is the type 2 bone morphogenetic protein (BMP2). Intestinal BMP2 homeostasis is directly involved in the maintenance of organ function. Thus, the aim of this study was to correlate the production of intestinal BMP2 with immunopathological changes in C57Bl\/6 mice infected with the <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic> Y strain in the acute and chronic phases. The mice were infected with 1000 blood trypomastigote forms. After euthanasia, the colon was collected, divided into two fragments, and a half was used for histological analysis and the other half for BMP2, IFN\u03b3, TNF-\u03b1, and IL-10 quantification. The infection induced increased intestinal IFN\u03b3 and BMP2 production during the acute phase as well as an increase in the inflammatory infiltrate. In contrast, a decreased number of neurons in the myenteric plexus were observed during this phase. Collagen deposition increased gradually throughout the infection, as demonstrated in the chronic phase. Additionally, a BMP2 increase during the acute phase was positively correlated with intestinal IFN\u03b3. In the same analyzed period, BMP2 and IFN\u03b3 showed negative correlations with the number of neurons in the myenteric plexus. As the first report of BMP2 alteration after infection by <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic>, we suggest that this imbalance is not only related to neuronal damage but may also represent a new route for maintaining the intestinal proinflammatory profile during the acute phase.<\/jats:p>","DOI":"10.1371\/journal.pone.0246692","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T01:13:51Z","timestamp":1612919631000},"page":"e0246692","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Correlation between intestinal BMP2, IFN\u03b3, and neural death in experimental infection with Trypanosoma cruzi"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-5112","authenticated-orcid":true,"given":"Jos\u00e9 Rodrigues","family":"do Carmo Neto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Vinicius da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarlla Loyane Lira","family":"Braga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Wilson","family":"Florencio da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone Gon\u00e7alves","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Resende Al\u00f4","family":"Nagib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-007X","authenticated-orcid":true,"given":"Mara R\u00fabia","family":"Nunes Celes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton Adriano Pelli","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Reis","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"issue":"6","key":"pone.0246692.ref001","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.mod.2005.03.003","article-title":"BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system","volume":"122","author":"AM Goldstein","year":"2005","journal-title":"Mech Dev"},{"issue":"4","key":"pone.0246692.ref002","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.cellsig.2010.10.003","article-title":"Bone Morphogenetic Proteins: A critical review","volume":"23","author":"B Bragdon","year":"2011","journal-title":"Cell Signal"},{"issue":"1","key":"pone.0246692.ref003","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ydbio.2010.11.017","article-title":"Bone morphogenetic proteins regulate enteric gliogenesis by modulating ErbB3 signaling","volume":"350","author":"A Chalazonitis","year":"2011","journal-title":"Dev Biol"},{"issue":"1","key":"pone.0246692.ref004","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/abbs\/gmx124","article-title":"The role of TGF-\u03b2 superfamily signaling in neurological disorders","volume":"50","author":"R Kashima","year":"2018","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"issue":"1","key":"pone.0246692.ref005","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/gcc.22502","article-title":"Transcription factors\u2014Intricate players of the bone morphogenetic protein signaling pathway","volume":"57","author":"M Ampuja","year":"2018","journal-title":"Genes Chromosom Cancer"},{"issue":"4","key":"pone.0246692.ref006","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/08977190412331279890","article-title":"Bone Morphogenetic Proteins","volume":"22","author":"D Chen","year":"2004","journal-title":"Growth Factors"},{"issue":"2","key":"pone.0246692.ref007","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.cell.2014.04.050","article-title":"Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility","volume":"158","author":"PA Muller","year":"2014","journal-title":"Cell"},{"key":"pone.0246692.ref008","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/901530","article-title":"Intestinal mucosal barrier is injured by BMP2\/4 via activation of NF- B signals after ischemic reperfusion.","volume":"2014","author":"K Chen","year":"2014","journal-title":"Mediators Inflamm"},{"issue":"1","key":"pone.0246692.ref009","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.immuni.2014.07.002","article-title":"Macrophages Have a Grip on the Gut","volume":"41","author":"M Locati","year":"2014","journal-title":"Immunity"},{"issue":"2","key":"pone.0246692.ref010","first-page":"529","article-title":"Expression analysis of BMP2, BMP5, BMP10 in human colon tissues from Hirschsprung disease patients","volume":"7","author":"M Wu","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"issue":"1\u20132","key":"pone.0246692.ref011","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.autneu.2011.06.003","article-title":"Neuronal loss and abnormal BMP\/Smad signaling in the myenteric plexus of diabetic rats","volume":"164","author":"SM Honor\u00e9","year":"2011","journal-title":"Auton Neurosci Basic Clin"},{"issue":"2","key":"pone.0246692.ref012","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/path.1976","article-title":"Altered bone morphogenetic protein signalling in the Helicobacter pylori-infected stomach","volume":"209","author":"SA Bleuming","year":"2006","journal-title":"J Pathol"},{"issue":"4","key":"pone.0246692.ref013","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00428-012-1299-7","article-title":"The significantly reduced number of interstitial cells of Cajal in chagasic megacolon (CM) patients might contribute to the pathophysiology of CM","volume":"461","author":"SJ Adad","year":"2012","journal-title":"Virchows Arch"},{"issue":"5","key":"pone.0246692.ref014","article-title":"Immunological Challenges to the Development of Chagasic Mega Syndromes","volume":"3","author":"EC Oliveira","year":"2018","journal-title":"Int J Cell Sci Mol Biol"},{"issue":"6","key":"pone.0246692.ref015","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1017\/S0031182007002296","article-title":"Morphometric study of eosinophils, mast cells, macrophages and fibrosis in the colon of chronic chagasic patients with and without megacolon","volume":"134","author":"ABM da Silveira","year":"2007","journal-title":"Parasitology"},{"issue":"8","key":"pone.0246692.ref016","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.humpath.2007.01.020","article-title":"Megacolon in Chagas disease: a study of inflammatory cells, enteric nerves, and glial cells","volume":"38","author":"ABM da Silveira","year":"2007","journal-title":"Hum Pathol"},{"issue":"4","key":"pone.0246692.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0153038","article-title":"Enteric neuronal damage, intramuscular denervation and smooth muscle phenotype changes as mechanisms of Chagasic megacolon: Evidence from a long-term murine model of tripanosoma cruzi infection","volume":"11","author":"CF Campos","year":"2016","journal-title":"PLoS One"},{"issue":"2","key":"pone.0246692.ref018","first-page":"289","article-title":"Interaction of human eosinophils or neutrophils with Trypanosoma cruzi in vitro causes bystander cardiac cell damage","volume":"66","author":"HA Molina","year":"1989","journal-title":"Immunology"},{"issue":"6","key":"pone.0246692.ref019","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s10620-018-5015-6","article-title":"Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence","volume":"63","author":"V Kannen","year":"2018","journal-title":"Dig Dis Sci"},{"issue":"1","key":"pone.0246692.ref020","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s13071-015-0811-8","article-title":"Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load","volume":"8","author":"BP Vazquez","year":"2015","journal-title":"Parasites and Vectors"},{"issue":"2","key":"pone.0246692.ref021","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/BF00548079","article-title":"Light and electron microscope studies of the autonomic nervous system in experimental and human American trypanosomiasis","volume":"354","author":"WL Tafuri","year":"1971","journal-title":"Virchows Arch Abteilung A Pathol Anat"},{"issue":"6","key":"pone.0246692.ref022","first-page":"443","article-title":"Pathological anatomy of chagasic megaesophagus","volume":"33","author":"SJ Adad","year":"1991","journal-title":"Rev Inst Med Trop Sao Paulo"},{"issue":"3","key":"pone.0246692.ref023","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s004280000319","article-title":"Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis","volume":"438","author":"SJ Adad","year":"2001","journal-title":"Virchows Arch"},{"issue":"5","key":"pone.0246692.ref024","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1017\/S0031182005008061","article-title":"Comparative study of the presence of Trypanosoma cruzi kDNA, inflammation and denervation in chagasic patients with and without megaesophagus","volume":"131","author":"ABM da SILVEIRA","year":"2005","journal-title":"Parasitology"},{"key":"pone.0246692.ref025","first-page":"224","volume":"111","author":"LBM Maifrino","year":"2005","journal-title":"Trypanosoma cruzi: Preliminary investigation of NADH-positive and somatostatin\u2013immunoreactive neurons in the myenteric plexus of the mouse colon during the infection"},{"key":"pone.0246692.ref026","first-page":"1","author":"K Kramer","year":"2011","journal-title":"Quantitative evaluation of neurons in the mucosal plexus of adult human intestines"},{"key":"pone.0246692.ref027","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nrgastro.2012.32","article-title":"The enteric nervous system and neurogastroenterology","volume":"9","author":"JB Furness","year":"2012","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"3","key":"pone.0246692.ref028","first-page":"1013","volume":"1","author":"MAR Freitas","year":"2017","journal-title":"Neurotrophin Expression in Chagasic Megacolon"},{"key":"pone.0246692.ref029","first-page":"389","article-title":"Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi","volume":"4","author":"Z BRENER","year":"1962","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"pone.0246692.ref030","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo-Jorge TC de, Castro SL de. Doen\u00e7a de chagas: manual para experimenta\u00e7\u00e3o animal. Doen\u00e7a de chagas: manual para experimenta\u00e7\u00e3o animal. Editora FIOCRUZ; 2000.","DOI":"10.7476\/9788575413937"},{"issue":"AUG","key":"pone.0246692.ref031","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.3389\/fmicb.2019.01856","article-title":"Correlation of parasite burden, kdna integration, autoreactive antibodies, and cytokine pattern in the pathophysiology of chagas disease","volume":"10","author":"M Wesley","year":"2019","journal-title":"Front Microbiol"},{"key":"pone.0246692.ref032","doi-asserted-by":"crossref","first-page":"648715","DOI":"10.1155\/2014\/648715","article-title":"Immunopathological aspects of experimental Trypanosoma cruzi reinfections","volume":"2014","author":"J Reis Machado","year":"2014","journal-title":"Biomed Res Int"},{"issue":"2","key":"pone.0246692.ref033","doi-asserted-by":"crossref","first-page":"e20180389","DOI":"10.1590\/0001-3765201920180389","article-title":"Effect of acetylsalicylic acid on total myenteric neurons in mice experimentally infected with Trypanosoma cruzi","volume":"91","author":"NDD Souza","year":"2019","journal-title":"An Acad Bras Cienc"},{"issue":"4","key":"pone.0246692.ref034","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/S0002-9440(10)63222-1","article-title":"Interferon-\u03b3-Induced Nitric Oxide Causes Intrinsic Intestinal Denervation in Trypanosoma cruzi-Infected Mice","volume":"164","author":"RME Arantes","year":"2004","journal-title":"Am J Pathol"},{"issue":"6","key":"pone.0246692.ref035","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/s00436-010-1794-1","article-title":"The role of selenium in intestinal motility and morphology in a murine model of Typanosoma cruzi infection","volume":"106","author":"AP De Souza","year":"2010","journal-title":"Parasitol Res"},{"issue":"4","key":"pone.0246692.ref036","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0014-4894(02)00024-3","article-title":"Trypanosoma cruzi: Role of host genetic background in the differential tissue distribution of parasite clonal populations","volume":"100","author":"LO Andrade","year":"2002","journal-title":"Exp Parasitol"},{"issue":"9","key":"pone.0246692.ref037","doi-asserted-by":"crossref","first-page":"e0008667","DOI":"10.1371\/journal.pntd.0008667","article-title":"NOD2 receptor is crucial for protecting against the digestive form of Chagas disease","volume":"14","author":"S Pereira N de","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"issue":"9","key":"pone.0246692.ref038","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.7150\/ijbs.7.1357","article-title":"Gastrointestinal infection with Mexican TcI Trypanosoma cruzi strains: Different degrees of colonization and diverse immune responses","volume":"7","author":"B Espinoza","year":"2011","journal-title":"Int J Biol Sci"},{"issue":"APR","key":"pone.0246692.ref039","doi-asserted-by":"crossref","first-page":"918","DOI":"10.3389\/fimmu.2019.00918","article-title":"An animal model of acute and chronic chagas disease with the reticulotropic Y strain of Trypanosoma cruzi that depicts the multifunctionality and dysfunctionality of T cells","volume":"10","author":"J Mateus","year":"2019","journal-title":"Front Immunol"},{"issue":"11","key":"pone.0246692.ref040","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.1111\/jcmm.13814","article-title":"BMP-2 induces human mononuclear cell chemotaxis and adhesion and modulates monocyte-to-macrophage differentiation","volume":"22","author":"E Pardali","year":"2018","journal-title":"J Cell Mol Med"},{"issue":"9\u201310","key":"pone.0246692.ref041","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1089\/ten.tea.2010.0555","article-title":"High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo","volume":"17","author":"JN Zara","year":"2011","journal-title":"Tissue Eng\u2014Part A"},{"issue":"3","key":"pone.0246692.ref042","doi-asserted-by":"crossref","first-page":"E149","DOI":"10.1097\/BRS.0b013e3181f2d1ec","article-title":"Inflammatory characteristics of rhBMP-2 in vitro and in an in vivo rodent model","volume":"36","author":"KB Lee","year":"2011","journal-title":"Spine (Phila Pa 1976)"},{"issue":"1","key":"pone.0246692.ref043","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12868-016-0314-3","article-title":"Bone morphogenetic protein-2-mediated pain and inflammation in a rat model of posterolateral arthrodesis","volume":"17","author":"K Mitchell","year":"2016","journal-title":"BMC Neurosci"},{"issue":"3","key":"pone.0246692.ref044","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1161\/CIRCRESAHA.116.308700","article-title":"BMP antagonist gremlin 2 limits inflammation after myocardial infarction","volume":"119","author":"LN Sanders","year":"2016","journal-title":"Circ Res"},{"issue":"1","key":"pone.0246692.ref045","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1089\/jir.2014.0199","article-title":"Inflammatory Cytokines Stimulate Bone Morphogenetic Protein-2 Expression and Release from Pancreatic Beta Cells","volume":"36","author":"A Ibarra Urizar","year":"2016","journal-title":"J Interf Cytokine Res"},{"key":"pone.0246692.ref046","doi-asserted-by":"crossref","first-page":"3421897","DOI":"10.1155\/2018\/3421897","article-title":"Upregulation of Cardiac IL-10 and Downregulation of IFN-\u03b3 in Balb\/c IL-4 \u2212\/\u2212 in Acute Chagasic Myocarditis due to Colombian Strain of Trypanosoma cruzi","volume":"2018","author":"MV Da Silva","year":"2018","journal-title":"Mediators Inflamm"},{"issue":"1","key":"pone.0246692.ref047","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1590\/S0074-02762009000100015","article-title":"Immunological imbalance between IFN-\u03b3 and IL-10 levels in the sera of patients with the cardiac form of Chagas disease","volume":"104","author":"DA D\u2019\u00c1vila","year":"2009","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pone.0246692.ref048","doi-asserted-by":"crossref","first-page":"683230","DOI":"10.1155\/2014\/683230","article-title":"Chagas disease cardiomyopathy: Immunopathology and genetics","volume":"2014","author":"E Cunha-Neto","year":"2014","journal-title":"Mediators Inflamm"},{"issue":"4","key":"pone.0246692.ref049","doi-asserted-by":"crossref","first-page":"e1630","DOI":"10.1371\/journal.pntd.0001630","article-title":"Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas\u2019 disease","volume":"6","author":"PMM Guedes","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"issue":"10","key":"pone.0246692.ref050","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1002\/eji.1830221006","article-title":"The microbicidal activity of interferon\u2010\u03b3\u2010treated macrophages against Trypanosoma cruzi involves an L\u2010arginine\u2010dependent, nitrogen oxide\u2010mediated mechanism inhibitable by interleukin\u201010 and transforming growth factor\u2010\u03b2","volume":"22","author":"RT Gazzinelli","year":"1992","journal-title":"Eur J Immunol"},{"issue":"11","key":"pone.0246692.ref051","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1128\/IAI.62.11.5177-5182.1994","article-title":"Nitric oxide is involved in control of Trypanosoma cruzi-induced parasitemia and directly kills the parasite in vitro","volume":"62","author":"GNR Vespa","year":"1994","journal-title":"Infect Immun"},{"issue":"2","key":"pone.0246692.ref052","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.4049\/jimmunol.0900047","article-title":"IL-17 Is Necessary for Host Protection against Acute-Phase Trypanosoma cruzi Infection","volume":"185","author":"Y Miyazaki","year":"2010","journal-title":"J Immunol"},{"issue":"1","key":"pone.0246692.ref053","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.nbd.2006.09.003","article-title":"Interferon-\u03b3 induced nitric oxide mediates in vitro neuronal damage by Trypanosoma cruzi-infected macrophages","volume":"25","author":"C Megale de Almeida-Leite","year":"2007","journal-title":"Neurobiol Dis"},{"issue":"4","key":"pone.0246692.ref054","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1590\/S0074-02762001000400017","article-title":"Morphometry of Submucous and Myenteric Esophagic Plexus of Dogs Experimentally Reinfected with Trypanosoma cruzi","volume":"96","author":"EMM Machado","year":"2001","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"2","key":"pone.0246692.ref055","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1590\/S0001-37652011000200014","article-title":"Neuronal changes caused by Trypanosoma cruzi: An experimental model","volume":"83","author":"NM Moreira","year":"2011","journal-title":"An Acad Bras Cienc"},{"issue":"6","key":"pone.0246692.ref056","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/iep.12049","article-title":"Moderate physical exercise reduces parasitaemia and protects colonic myenteric neurons in mice infected with Trypanosoma cruzi","volume":"94","author":"NM Moreira","year":"2013","journal-title":"Int J Exp Pathol"},{"issue":"2","key":"pone.0246692.ref057","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1590\/S0074-02761996000200018","article-title":"Trypanosoma cruzi Strains and Autonomic Nervous System Pathology in Experimental Chagas Disease","volume":"91","author":"MM De Souza","year":"1996","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"2","key":"pone.0246692.ref058","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000258689","article-title":"\u2019Imp\u00e9rio Lima MR, Chadi G, \u00c1lvarez JM. Neurodegeneration and increased production of nitrotyrosine, nitric oxide synthase, IFN-\u03b3 and s100\u03b2 protein in the spinal cord of IL-12p40-deficient mice infected with Trypanosoma cruzi","volume":"17","author":"D Bombeiro AL","year":"2010","journal-title":"Neuroimmunomodulation"},{"issue":"6","key":"pone.0246692.ref059","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1096\/fj.07-099499","article-title":"Interferon\u2010\u03b3 directly induces neurotoxicity through a neuron specific, calcium\u2010permeable complex of IFN\u2010\u03b3 receptor and AMPA GluRl receptor","volume":"22","author":"T Mizuno","year":"2008","journal-title":"FASEB J"},{"key":"pone.0246692.ref060","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/bs.apha.2017.09.003","article-title":"Nitric Oxide Signaling in Neurodegeneration and Cell Death","volume":"82","author":"TM Dawson","year":"2018","journal-title":"Adv Pharmacol"},{"issue":"1","key":"pone.0246692.ref061","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/toxsci\/kfx124","article-title":"From the Cover: Arsenic Induces Hippocampal Neuronal Apoptosis and Cognitive Impairments via an Up-Regulated BMP2\/Smad-Dependent Reduced BDNF\/TrkB Signaling in Rats","volume":"159","author":"R Pandey","year":"2017","journal-title":"Toxicol Sci"},{"issue":"12","key":"pone.0246692.ref062","doi-asserted-by":"crossref","first-page":"e83067","DOI":"10.1371\/journal.pone.0083067","article-title":"Role of miR-17 family in the negative feedback loop of bone morphogenetic protein signaling in neuron","volume":"8","author":"Q Sun","year":"2013","journal-title":"PLoS One"},{"issue":"SUPPL. 1","key":"pone.0246692.ref063","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1590\/S0074-02762009000900025","article-title":"Back to the future in Chagas disease: From animal models to patient cohort studies, progress in immunopathogenesis research","volume":"104","author":"J Scharfstein","year":"2009","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"3","key":"pone.0246692.ref064","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00418-014-1250-x","article-title":"Chagasic megacolon: Enteric neurons and related structures","volume":"142","author":"S Jabari","year":"2014","journal-title":"Histochem Cell Biol"},{"key":"pone.0246692.ref065","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.3389\/fimmu.2018.01842","article-title":"Autoimmunity in chronic chagas disease: A road of multiple pathways to cardiomyopathy?.","volume":"9","author":"E De Bona","year":"2018","journal-title":"Front Immunol"},{"key":"pone.0246692.ref066","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev-pathol-020117-043711","article-title":"Pathology and Pathogenesis of Chagas Heart Disease","volume":"14","author":"KM Bonney","year":"2019","journal-title":"Annu Rev Pathol"},{"issue":"10","key":"pone.0246692.ref067","doi-asserted-by":"crossref","first-page":"e592","DOI":"10.1111\/codi.12331","article-title":"Interstitial cells of Cajal: Crucial for the development of megacolon in human Chagas\u2019 disease?","volume":"15","author":"S Jabari","year":"2013","journal-title":"Color Dis"},{"issue":"9","key":"pone.0246692.ref068","doi-asserted-by":"crossref","first-page":"G804","DOI":"10.1152\/ajpgi.00306.2012","article-title":"BMP2 inhibits TGF-\u03b2-induced pancreatic stellate cell activation and extracellular matrix formation","volume":"304","author":"X Gao","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"2","key":"pone.0246692.ref069","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1210\/en.2008-0090","article-title":"Bone morphogenetic protein-2 antagonizes renal interstitial fibrosis by promoting catabolism of type i transforming growth factor-\u03b2 receptors","volume":"150","author":"YL Yang","year":"2009","journal-title":"Endocrinology"},{"issue":"3","key":"pone.0246692.ref070","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1164\/rccm.200706-945OC","article-title":"Gremlin-mediated decrease in bone morphogenetic protein signaling promotes pulmonary fibrosis","volume":"177","author":"M Myll\u00e4rniemi","year":"2008","journal-title":"Am J Respir Crit Care Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246692","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T01:14:31Z","timestamp":1612919671000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246692"}},"subtitle":[],"editor":[{"given":"Rossana C.N.","family":"Melo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,9]]},"references-count":70,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0246692","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,9]]}}}