{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:28Z","timestamp":1785430468563,"version":"3.56.0"},"reference-count":96,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI159450,UL1TR002345"],"award-info":[{"award-number":["AI159450,UL1TR002345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["8042-32000-116-000-D"],"award-info":[{"award-number":["8042-32000-116-000-D"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Trichuriasis, caused by the parasitic nematode\n                      <jats:italic toggle=\"yes\">Trichuris trichiura<\/jats:italic>\n                      , affects 429\u2013508 million people worldwide. Although the early phase of whipworm infection is crucial for establishing infection, its underlying molecular mechanisms remain unclear. In this study, we examined and compared host transcriptional responses during early infection of the mouse whipworm,\n                      <jats:italic toggle=\"yes\">T. muris<\/jats:italic>\n                      , using first-stage larvae (L1) in proximal colons from\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      models (B6 and STAT6-deficient mice) and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      colonoid models. Differentially expressed genes and functional enrichment analysis revealed that while the \u201cneurotransmitter release\u201d pathway was uniquely upregulated in B6 mice, the \u201clipid metabolism\u201d pathway was commonly modulated in both mice and colonoids, which may have implications for intestinal epithelial function during infection. Enrichment of alternative splicing (AS) events in splicing-related pathways across all models highlighted the need for further investigation into AS regulation mechanisms and its functional roles during early infection. Temporal transcriptomic profiling of L1\n                      <jats:italic toggle=\"yes\">T. muris<\/jats:italic>\n                      in colonoids identified six clusters representing fundamental molecular pathways associated with parasite development and adaptation. Utilizing dual-RNA sequencing from infected colonoids, we conducted host\u2013parasite co-expression analysis, identifying correlated gene pairs, including a negative correlation between\n                      <jats:italic toggle=\"yes\">T. muris<\/jats:italic>\n                      -secreted serine proteases and mouse genes involved in metabolism and epithelial cell functions. These findings provide valuable insights into the dynamic transcriptional regulation during early L1\n                      <jats:italic toggle=\"yes\">T. muris<\/jats:italic>\n                      infection\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , offering a resource for comparative studies in whipworm infection models. In conclusion, this comparative study serves as a starting point for deeper investigation into molecular mechanisms underlying early whipworm infection and opens up new opportunities for exploring host\u2013parasite interactions.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Trichuriasis, caused by the parasitic nematode\n                        <jats:italic toggle=\"yes\">Trichuris trichiura<\/jats:italic>\n                        , remains a major public health concern, particularly in resource-limited regions. Current anthelmintics show suboptimal efficacy against whipworm infections, highlighting the critical need for novel therapeutic strategies. This study provides a comparative framework by integrating transcriptional profiles from\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        models during the early infection phase of\n                        <jats:italic toggle=\"yes\">T. muris<\/jats:italic>\n                        , a mouse model for\n                        <jats:italic toggle=\"yes\">T. trichiura<\/jats:italic>\n                        . Through this approach, we demonstrate the potential of proximal colonoids as a model for investigating key aspects of host\u2013parasite interactions, including epithelial invasion and transcriptional dynamics, during early\n                        <jats:italic toggle=\"yes\">T. muris<\/jats:italic>\n                        infection. By employing dual-RNA sequencing, we not only characterize temporal gene expression dynamics of first-stage larvae but also identify host\u2013parasite co-expression profiles, thereby shedding light on molecular pathways that may underlie infection establishment and host responses. This work builds upon and solidifies previous findings about the utility of organoid models for investigating early whipworm infection while providing a foundational resource for exploring intervention strategies targeting the initial stages of infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02176-25","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T13:03:13Z","timestamp":1757595793000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptional responses of mouse proximal colon and colonoids during early whipworm infection"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1083-2882","authenticated-orcid":false,"given":"Hyeim","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Washington University School of Medicine","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Joseph F.","family":"Urban","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03b08sh51","id-type":"ROR","asserted-by":"publisher"}],"name":"United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasite Diseases Laboratory and Beltsville Human Nutrition Research Center, Diet, Genomics and Immunology Laboratory","place":["Beltsville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Washington University School of Medicine","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9572-3436","authenticated-orcid":true,"given":"Makedonka","family":"Mitreva","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Washington University School of Medicine","place":["St. Louis, USA"]},{"name":"McDonnell Genome Institute, Washington University School of Medicine","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68653-4"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"e_1_3_5_4_2","first-page":"972","article-title":"Efficacy of albendazole against the whipworm Trichuris trichiura--a randomised, controlled trial","volume":"94","author":"Adams VJ","year":"2004","unstructured":"Adams VJ, Lombard CJ, Dhansay MA, Markus MB, Fincham JE. 2004. Efficacy of albendazole against the whipworm Trichuris trichiura--a randomised, controlled trial. S Afr Med J 94:972\u2013976.","journal-title":"S Afr Med J"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-199809000-00011"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(90)90227-u"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100335"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-012-0348-2"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(04)57004-5"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2011.12.001"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid3101.240995"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","unstructured":"B\u00e4r MA Kouam\u00e9 NA Tour\u00e9 S Coulibaly JT Schneeberger PHH Keiser J. 2025. Genomic and morphological characterization of Trichuris incognita a human-infecting trichuris species. bioRxiv. doi:10.1101\/2024.06.11.598441","DOI":"10.1101\/2024.06.11.598441"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.a.214"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10080925"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646738"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.637570"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm131"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29334-0"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.015"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1428004"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.06.001"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","unstructured":"White R Berm\u00fadez-Barrientos JR Robertson E Duque Correa MA Buck AH. 2024. 2-D organoids demonstrate specificity in the interactions of parasitic nematodes and their secreted products at the basal or apical intestinal epithelium. bioRxiv. doi:10.1101\/2024.12.16.628471","DOI":"10.1101\/2024.12.16.628471"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-024-01313-4"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07509"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002621"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.05.025"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf492"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10288"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-38879-z"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0144"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101737"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2338"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0323"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25173935"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a022094"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3012"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-7-53"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74540-9"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.6026\/97320630002005"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.02.009"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-12-08408.1995"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200203055"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012502"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0262-1"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005840"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001856"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2022.151976"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107926"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins4111196"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1385\/ep:14:1:3"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35241-6"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2613.2011.00767.x"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-0954-z"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01489"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.73"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.04.009"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.10.014"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21096"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2004.08.005"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.2955"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2024.06.014"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.04.018"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.023"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1648"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02557"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.411"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1086\/339005"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0171-3"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.951535"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.3.1146"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.1017\/s0022149x00009160"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.06.005"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-69462-5"},{"key":"e_1_3_5_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.153"},{"key":"e_1_3_5_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1049"},{"key":"e_1_3_5_78_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_3_5_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1019"},{"key":"e_1_3_5_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn698"},{"key":"e_1_3_5_81_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp101"},{"key":"e_1_3_5_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt019"},{"key":"e_1_3_5_83_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_3_5_84_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419161111"},{"key":"e_1_3_5_85_2","doi-asserted-by":"publisher","DOI":"10.3892\/br.2014.407"},{"key":"e_1_3_5_86_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu031"},{"key":"e_1_3_5_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2015.11.006"},{"key":"e_1_3_5_88_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky350"},{"key":"e_1_3_5_89_2","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/dsu001"},{"key":"e_1_3_5_90_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7015-5_6"},{"key":"e_1_3_5_91_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4315"},{"key":"e_1_3_5_92_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1134"},{"key":"e_1_3_5_93_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-421"},{"key":"e_1_3_5_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01101-x"},{"key":"e_1_3_5_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"},{"key":"e_1_3_5_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2016.11.005"},{"key":"e_1_3_5_97_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz401"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02176-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02176-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:04:19Z","timestamp":1759928659000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.02176-25"}},"subtitle":[],"editor":[{"given":"Gong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":96,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,8]]}},"alternative-id":["10.1128\/mbio.02176-25"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02176-25","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]},"assertion":[{"value":"2025-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02176-25"}}