{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:14:14Z","timestamp":1753892054477,"version":"3.41.2"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Parasitol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Eimeria pragensis<\/jats:italic>, an intestinal protozoa infecting mice, induces colitis and reduces goblet cell numbers in the large intestine. In the present study, we investigated the pathogenesis and the mechanisms underlying goblet cell down-regulation in the early phase of infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL\/6 mice were orally infected with 300 oocysts. Fecal oocyst shedding and body weight were monitored daily. Colon tissues were collected at 3, 8, and 13 days post-infection (dpi) to assess pathological changes. Parasite burden was assessed by histological analysis (H&amp;amp;E staining) and qPCR targeting 5S rRNA. Goblet cells were visualized using PAS-Alcian Blue staining and Muc2 immunohistochemistry. To elucidate mechanisms of goblet cell dysfunction, we performed RNA sequencing of large intestine tissue to examine host as well as parasite transcriptomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fecal oocyst excretion peaked at 8\u20139 dpi. Body weight decreased from 6 to 11 dpi, with recovery after 12 dpi. Maximal parasite accumulation in the proximal colon was observed at 8 dpi in histological examination as well as qPCR. Colon length was significantly shortened at 3 dpi. Goblet cell area significantly reduced at 8 dpi (p &amp;lt; 0.05). RNA sequencing of infected large intestines revealed that <jats:italic>E. pragensis<\/jats:italic> produced enzymes that were known to degrade mucin and tight junctions, and proteins that could activate the Notch\u2013Hes1 signaling pathway. As for host responses, genes associated with Th1-type inflammation, epithelial barrier disruption, and immune regulation were up-regulated as early as 3 dpi.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings suggested that <jats:italic>E. pragensis<\/jats:italic> infection induces a mucosal barrier dysfunction in the early phase of the infection, which possibly causes the tissue invasion of bacteria in the large intestine. Th1-type inflammatory response, thus induced, reduces goblet cell numbers and mucin production. This model provides valuable insight into the mechanisms of mucosal barrier disruption during protozoan infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpara.2025.1621486","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T05:21:49Z","timestamp":1750742509000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Down-regulation of colon mucin production induced by Eimeria pragensis infection in mice"],"prefix":"10.3389","volume":"4","author":[{"given":"Yulia Dwi","family":"Setia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mio","family":"Kokubo-Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryusei","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akemi","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Nagayasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parnian","family":"Ahmadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruhiko","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10091154","article-title":"An exaggerated immune response in female Balb\/c mice controls initial Toxoplasma gondii multiplication but increases mortality and morbidity relative to male mice","volume":"10","author":"Alonaizan","year":"2021","journal-title":"Pathogens"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1182\/blood-2009-06-224782","article-title":"TAK1 targeting by glucocorticoids determines JNK\u00a0and I\u03baB regulation in toll-like receptor-stimulated macrophages","volume":"115","author":"Bhattacharyya","year":"2010","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.pt.2013.10.003","article-title":"Securing poultry production from the ever-present Eimeria challenge","volume":"30","author":"Blake","year":"2014","journal-title":"Trends in Parasitology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.ijpara.2005.09.011","article-title":"Eimeria maxima: The influence of host genotype on parasite reproduction as revealed by quantitative real-time PCR","volume":"36","author":"Blake","year":"2006","journal-title":"International Journal for Parasitology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78141-4","article-title":"Mucin-2 knockout is a model of intercellular junction defects, mitochondrial damage and ATP depletion in the intestinal epithelium","volume":"10","author":"Borisova","year":"2020","journal-title":"Sci. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1017\/S0031182019001562","article-title":"Life cycle stages, specific organelles and invasion mechanisms of Eimeria species","volume":"147","author":"Burrell","year":"2020","journal-title":"Parasitology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1111\/j.1365-2982.2012.01921.x","article-title":"Intestinal barrier function in health and gastrointestinal disease","volume":"24","author":"Camilleri","year":"2012","journal-title":"Neurogastroenterol. Motility."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61299-6","article-title":"Effects of Eimeria acervulina infection on the luminal and mucosal microbiota of the cecum and ileum in broiler chickens","volume":"14","author":"Campos","year":"2024","journal-title":"Sci. Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3382\/ps.2013-03634","article-title":"Milestones in avian coccidiosis research: A review","volume":"93","author":"Chapman","year":"2014","journal-title":"Poultry Science."},{"key":"B11","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.pt.2016.08.007","article-title":"Are eimeria genetically diverse, and does it matter","volume":"33","author":"Clark","year":"2017","journal-title":"Trends Parasitology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/s11739-023-03374-w","article-title":"Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review","volume":"19","author":"Di Vincenzo","year":"2024","journal-title":"Internal Emergency Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s00436-014-4192-2","article-title":"Sex-determined susceptibility and differential MUC2 mRNA\u00a0expression during the course of murine intestinal eimeriosis","volume":"114","author":"Dkhil","year":"2015","journal-title":"Parasitol. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/439865","article-title":"Goblet cells and mucin related gene expression in mice infected with Eimeria papillate","volume":"2003","author":"Dkhil","year":"2013","journal-title":"Sci. World J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-4095-6","article-title":"Dual RNA-seq reveals no plastic transcriptional response of the coccidian parasite Eimeria falciformis to host immune defenses","volume":"18","author":"Ehret","year":"2017","journal-title":"BMC Genomics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2412676","article-title":"Giardia spp.-induced microbiota dysbiosis disrupts intestinal mucin glycosylation","volume":"16","author":"Fekete","year":"2024","journal-title":"Gut Microbes"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21769\/bioprotoc.3122","article-title":"Eimeria vermiformis infection model of murine small intestine","volume":"8","author":"Figueiredo-Campos","year":"2018","journal-title":"Bio-Protocol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/nature03589","article-title":"Notch signals control the fate of immature progenitor cells in the intestine","volume":"435","author":"Fre","year":"2005","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00638-21","article-title":"Dual transcriptomics to determine gamma interferon- independent host response to intestinal cryptosporidium parvum infection","volume":"90","author":"Gallego-Lopez","year":"2022","journal-title":"Infection Immunity."},{"key":"B22","doi-asserted-by":"publisher","first-page":"486","DOI":"10.5812\/ijem.3505","article-title":"Normality tests for statistical analysis: A guide for non-statisticians","volume":"10","author":"Ghasemi","year":"2012","journal-title":"Int. J. Endocrinol. Metab."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030169","article-title":"A novel PAN\/apple domain-containing protein from Toxoplasma gondii: Characterization and receptor identification","volume":"7","author":"Gong","year":"2012","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02054","article-title":"Mucins in intestinal mucosal defense and inflammation: learning from clinical and experimental studies","volume":"11","author":"Grondin","year":"2020","journal-title":"Front. Immunol."},{"key":"B25","doi-asserted-by":"crossref","DOI":"10.1016\/j.pt.2024.09.008","article-title":"Eimeria falciformis","volume-title":"Trends in Parasitology","author":"G\u00fcnay-Esiyok","year":"2024"},{"key":"B26","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/s41575-022-00675-x","article-title":"The role of goblet cells and mucus in intestinal homeostasis","volume":"19","author":"Gustafsson","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatology."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001856","article-title":"Serine protease(s) secreted by the nematode Trichuris muris degrade the mucus barrier","volume":"6","author":"Hasnain","year":"2012","journal-title":"PloS Negl. Trop. Diseases."},{"key":"B28","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1055\/s-0035-1547335","article-title":"Parasitic colitis","volume":"28","author":"Hechenbleikner","year":"2015","journal-title":"Clinics Colon Rectal Surg."},{"key":"B29","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1111\/fcp.12894","article-title":"Phosphatidylinositol 3-kinase signaling pathway and inflammatory bowel disease: Current status and future prospects","volume":"37","author":"Jalil","year":"2023","journal-title":"Fundam. Clin. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.886781","article-title":"Time-series transcriptome analysis identified differentially expressed genes in broiler chicken infected with mixed Eimeria species","volume":"13","author":"Kim","year":"2022","journal-title":"Front. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s11894-010-0131-2","article-title":"Intestinal goblet cells and mucins in health and disease: Recent insights and progress","volume":"12","author":"Kim","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2005.12.007","article-title":"The real-time polymerase chain reaction","volume":"27","author":"Kubista","year":"2006","journal-title":"Molecular Aspects of Medicine"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0281516","article-title":"Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response","volume":"18","author":"Kyunai","year":"2023","journal-title":"PloS One"},{"key":"B35","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1080\/19490976.2019.1614363","article-title":"The delicate balance between Entamoeba histolytica, mucus and microbiota","volume":"11","author":"Leon-Coria","year":"2020","journal-title":"Gut Microbes"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.ppat.1007466","article-title":"Defining cooperative roles for colonic microbiota and Muc2 mucin in mediating innate host defense against Entamoeba histolytica","volume":"14","author":"Leon-Coria","year":"2018","journal-title":"PloS Pathogens."},{"key":"B37","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1038\/s43018-020-0095-6","article-title":"Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity","volume":"1","author":"Li","year":"2020","journal-title":"Nat. cancer."},{"key":"B38","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00823-24","article-title":"Dynamic response of the intestinal microbiome to Eimeria maxima- induced\u00a0coccidiosis in chickens","volume":"12","author":"Liu","year":"2024","journal-title":"Microbiol. Spectrum"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12864-016-2632-3","article-title":"Comparative genomics reveals Cyclospora cayetanensis possesses coccidia-like metabolism and invasion components but unique surface antigens","volume":"17","author":"Liu","year":"2016","journal-title":"BMC Genomics"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.751481","article-title":"Coccidia-microbiota interactions and their effects on the host","volume":"11","author":"Lu","year":"2021","journal-title":"Front. Cell. Infection Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nri1056","article-title":"PI3K in lymphocyte development,\u00a0differentiation and activation","volume":"3","author":"Okkenhaug","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/imr.12182","article-title":"The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system","volume":"260","author":"Pelaseyed","year":"2014","journal-title":"Immunol. Rev."},{"key":"B44","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1186\/s12967-024-05673-y","article-title":"Interferon regulatory\u00a0factor 7 alleviates the experimental colitis through enhancing IL-28A-mediated intestinal epithelial integrity","volume":"22","author":"Qing","year":"2024","journal-title":"J. Trans. Med."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2009","journal-title":"Bioinformatics."},{"key":"B46","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"B47","article-title":"Eimeria pragensis induce immune mediated intestinal hypomotility in C57BL\/6 mice","volume-title":"Proceedings of the 20th FAVA Congress &amp; The 15th KIVNAS PDHI, Bali Nov 1\u20133, 2018","author":"Siswandi","year":"2018"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1292\/jvms.19-0137","article-title":"X-ray evaluation of intestinal dysmotility induced by Eimeria pragensis infection in C57BL\/6 mice","volume":"81","author":"Siswandi","year":"2019","journal-title":"J. Veterinary Med. Sci."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00130-24","article-title":"Study on the alleviative effect of Lactobacillus plantarum on Eimeria falciformis infection","volume":"92","author":"Sun","year":"2024","journal-title":"Infection Immunity."},{"key":"B50","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1111\/bjh.16871","article-title":"All-trans-retinoic acid shifts Th1 towards Th2 cell differentiation by targeting NFAT1 signalling to ameliorate immune-mediated aplastic anaemia","volume":"191","author":"Tang","year":"2020","journal-title":"Br. J. Haematology."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2021.102521","article-title":"Eimeria pragensis infection alters the gut microenvironment to favor extrinsic shiga toxin-producing Escherichia coli O157:H7 colonization in mice","volume":"87","author":"Uemura","year":"2022","journal-title":"Parasitol. Int."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006033","article-title":"Resolving host\u2013pathogen interactions by dual RNA-seq","volume":"13","author":"Westermann","year":"2017","journal-title":"PloS Pathog"},{"key":"B53","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1292\/jvms.67.311","article-title":"Murine goblet cell hypoplasia during Eimeria pragensis infection is ameliorated by clindamycin treatment","volume":"67","author":"Yunus","year":"2005","journal-title":"J. Veterinary Med. Sci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1292\/jvms.67.165","article-title":"The relationship between the anticoccidial effects of clindamycin and the development of immunity in the Eimeria pragensis\/mouse model of large intestinal coccidiosis","volume":"67","author":"Yunus","year":"2005","journal-title":"J. Veterinary Med. Sci."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.832672","article-title":"Crosstalk between the gut microbiota and epithelial cells under physiological and infectious conditions","volume":"12","author":"Zhou","year":"2022","journal-title":"Front. Cell. Infection Microbiol."}],"container-title":["Frontiers in Parasitology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpara.2025.1621486\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T05:21:51Z","timestamp":1750742511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpara.2025.1621486\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":55,"alternative-id":["10.3389\/fpara.2025.1621486"],"URL":"https:\/\/doi.org\/10.3389\/fpara.2025.1621486","relation":{},"ISSN":["2813-2424"],"issn-type":[{"type":"electronic","value":"2813-2424"}],"subject":[],"published":{"date-parts":[[2025,6,24]]},"article-number":"1621486"}}