{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:13:19Z","timestamp":1792113199317,"version":"4.4.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK126969"],"award-info":[{"award-number":["R01DK126969"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK132327"],"award-info":[{"award-number":["R01DK132327"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK30292"],"award-info":[{"award-number":["R01DK30292"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000875","name":"Pew Charitable Trusts","doi-asserted-by":"publisher","award":["00035299"],"award-info":[{"award-number":["00035299"]}],"id":[{"id":"10.13039\/100000875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/06577-9"],"award-info":[{"award-number":["2017\/06577-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/15313-8"],"award-info":[{"award-number":["2018\/15313-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:p>\n                    <jats:italic>Clostridioides difficile<\/jats:italic>\n                    infection (CDI) is a common cause of antibiotic-associated colitis.\n                    <jats:italic>C. difficile<\/jats:italic>\n                    proliferates and produces toxins that damage the colonic epithelium, leading to symptoms ranging from mild diarrhea to severe pseudomembranous colitis. The host\u2019s innate response to CDI occurs in two phases: an early phase in which neutrophils reduce the bacterial load and a late phase involving repair mechanisms to restore epithelial integrity. Group 3 innate lymphoid cells (ILC3s) are crucial in protecting the gut from CDI. Previous studies have shown that ILC3-derived IL-22 is essential in the late phase of CDI for epithelial repair and maintaining an intestinal microbiota that competes with\n                    <jats:italic>C. difficile<\/jats:italic>\n                    , preventing its expansion. Our study finds that ILC3s also protect during the early stages of CDI by sustaining neutrophils through GM-CSF. Less neutrophil production, accumulation, and activation was evident in ILC3-deficient mice than in wild-type (WT) mice, which led to exacerbated symptoms, impaired pathogen clearance, a compromised epithelial barrier, and increased mortality. The adoptive transfer of ILC3s into ILC3-deficient mice restored neutrophil responses and improved disease outcomes. Both in vitro and in vivo experiments revealed that GM-CSF production by ILC3s is crucial for neutrophil production and effective resistance during CDI. Using mice lacking NKp46\n                    <jats:sup>+<\/jats:sup>\n                    ILC3s, we found that this subset significantly contributes to GM-CSF production in CDI. These findings highlight the critical role of the ILC3-neutrophil connection in early innate responses to CDI. Enhancing ILC3 production of GM-CSF could be a promising strategy for improving host defense against CDI and other enteric infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2416182121","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T14:02:39Z","timestamp":1730296959000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["NKp46\n                    <sup>+<\/sup>\n                    ILC3s promote early neutrophil defense against\n                    <i>Clostridioides difficile<\/i>\n                    infection through GM-CSF secretion"],"prefix":"10.1073","volume":"121","author":[{"given":"Jos\u00e9 L.","family":"Fachi","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1672-0996","authenticated-orcid":false,"given":"Susan","family":"Gilfillan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Ulezko","family":"Antonova","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinChao","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A. R.","family":"Vinolo","sequence":"additional","affiliation":[{"name":"Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-4987","authenticated-orcid":false,"given":"Marco","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.108"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.20"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000989"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-020-01980-x"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4114"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux048"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00660-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-019-03539-6"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003761"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200821"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.025"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.07.008"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10066"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2356"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062505"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12020273"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190489"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.06.011"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.017"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.05.013"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07537"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa6566"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.005"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.017"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20122097"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11813"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1249288"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.11.011"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2187"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2014.02.001"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.2016004"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1710"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00703.x"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0412-0"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S262566"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V68.3.708.708"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq434"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107857"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91894"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.154"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151403"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00236-23"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2016.04.001"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11304-8"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.10"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0282-9"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0425-y"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2416182121"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2416182121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T14:04:23Z","timestamp":1730297063000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2416182121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":48,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2024,11,5]]}},"alternative-id":["10.1073\/pnas.2416182121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2416182121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]},"assertion":[{"value":"2024-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2416182121"}}