{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:23:31Z","timestamp":1792290211796,"version":"4.4.0"},"reference-count":97,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2119968"],"award-info":[{"award-number":["2119968"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2025,5,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Bacteriophages are the dominant members of the human enteric virome and can shape bacterial communities in the gut; however, our understanding of how they directly impact health and disease is limited. Previous studies have shown that specific bacteriophage populations are expanded in patients with Crohn\u2019s disease (CD) and ulcerative colitis (UC), suggesting that fluctuations in the enteric virome may contribute to intestinal inflammation. Based on these studies, we hypothesized that a high bacteriophage burden directly induces intestinal epithelial responses. We found that filamentous bacteriophages M13 and Fd induced dose-dependent IL-8 expression in the human intestinal epithelial cell line HT-29 to a greater degree than their lytic counterparts, T4 and \u03d5X174. We also found that M13, but not Fd, reduced bacterial internalization in HT-29 cells. This led us to investigate the mechanism underlying M13-mediated inhibition of bacterial internalization by examining the antiviral and antimicrobial responses in these cells. M13 upregulated type I and III IFN expressions and augmented short-chain fatty acid (SCFA)-mediated LL-37 expression in HT-29 cells. Taken together, our data establish that filamentous bacteriophages directly affect human intestinal epithelial cells. These results provide new insights into the complex interactions between bacteriophages and the intestinal mucosa, which may underlie disease pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00618-24","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T09:43:21Z","timestamp":1744278201000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Filamentous bacteriophage M13 induces proinflammatory responses in intestinal epithelial cells"],"prefix":"10.1128","volume":"93","author":[{"given":"Ambarish C.","family":"Varadan","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California","place":["Merced, USA"]},{"name":"Quantitative and Systems Biology Graduate Group, University of California","place":["Merced, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3945-0135","authenticated-orcid":true,"given":"Juris A.","family":"Grasis","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California","place":["Merced, USA"]},{"name":"Quantitative and Systems Biology Graduate Group, University of California","place":["Merced, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00536-5"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02248-18"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.04.018"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.10.009"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0210-y"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa094"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.06.056"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1706359114"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.07.005"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007370"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4380"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.01.004"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abn6660"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2014.10.006"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.05.001"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.20.6220-6223.2003"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09199"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00061-19"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-318131"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2614"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9691"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.01.008"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08336-9"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-019-0250-5"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(89)90024-x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.08.008"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13030455"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.11.016"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8451"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14983"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2019.1701353"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-023-01496-z"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0510-x"},{"key":"e_1_3_4_36_2","first-page":"51","article-title":"Filamentous bacteriophage: biology, phage display and nanotechnology applications","volume":"13","author":"Rakonjac J","year":"2011","unstructured":"Rakonjac J, Bennett NJ, Spagnuolo J, Gagic D, Russel M. 2011. Filamentous bacteriophage: biology, phage display and nanotechnology applications. Curr Issues Mol Biol 13:51\u201376. https:\/\/doi.org\/10.21775\/cimb.013.051.","journal-title":"Curr Issues Mol Biol"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.10.013"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006495"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100656"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0800224"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-164-6_7"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.2261"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-565-1_13"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1585"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3292"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700661"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0300-9084(86)80177-8"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-16104-4"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.061168"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)91064-o"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.01.007"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.03.012"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199801000-00013"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1609"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-200104000-00011"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.6.3503-3511.2003"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90436-0"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.3390\/v15081726"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/v16010165"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-5956-6-13"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.9.4147"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.17193"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.12.016"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.608645"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1206"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mucimm.2023.06.004"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003727"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39481"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305923110"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/415389a"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2206"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1180"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.12.6718"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.5.735"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.10.008"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0157-3"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.28.10.1221"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01179-1"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002566"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01112"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01614"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1002\/mbo3.384"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291x(76)90824-x"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3700-2"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-018-1873-6"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.4137\/CGast.S20612"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2298"},{"key":"e_1_3_4_88_2","first-page":"276","article-title":"Effect of LPS on epithelial integrity and bacterial uptake in the polarized human enterocyte-like cell line Caco-2","volume":"40","author":"Wells CL","year":"1993","unstructured":"Wells CL, Jechorek RP, Olmsted SB, Erlandsen SL. 1993. Effect of LPS on epithelial integrity and bacterial uptake in the polarized human enterocyte-like cell line Caco-2. Circ Shock 40:276\u2013288.","journal-title":"Circ Shock"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199406000-00009"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/170.6.1549"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071036"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2011.21"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.123862"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2116197119"},{"key":"e_1_3_4_95_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2331520"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201400508"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02057-3"},{"key":"e_1_3_4_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1286-4579(00)90356-3"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00618-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00618-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T09:01:14Z","timestamp":1747126874000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00618-24"}},"subtitle":[],"editor":[{"given":"Igor E.","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":97,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,13]]}},"alternative-id":["10.1128\/iai.00618-24"],"URL":"https:\/\/doi.org\/10.1128\/iai.00618-24","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]},"assertion":[{"value":"2024-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00618-24"}}