{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:53:58Z","timestamp":1781103238894,"version":"3.54.1"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"51","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["F31 AI156949"],"award-info":[{"award-number":["F31 AI156949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI042347"],"award-info":[{"award-number":["R01 AI042347"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100000011","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":[[2023,12,19]]},"abstract":"<jats:p>\n                    Systemic infections can yield distinct outcomes in different tissues. In mice, intravenous inoculation of\n                    <jats:italic toggle=\"yes\">Escherichia<\/jats:italic>\n                    <jats:italic toggle=\"yes\">coli<\/jats:italic>\n                    leads to bacterial replication within liver abscesses, while other organs such as the spleen clear the pathogen. Abscesses are macroscopic necrotic regions that comprise the vast majority of the bacterial burden in the animal, yet little is known about the processes underlying their formation. Here, we characterize\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    liver abscesses and identify host determinants of abscess susceptibility. Spatial transcriptomics revealed that liver abscesses are associated with heterogenous immune cell clusters comprised of macrophages, neutrophils, dendritic cells, innate lymphoid cells, and T-cells that surround necrotic regions of the liver. Abscess susceptibility is heightened in the C57BL lineage, particularly in C57BL\/6N females. Backcross analyses demonstrated that abscess susceptibility is a polygenic trait inherited in a sex-dependent manner without direct linkage to sex chromosomes. As early as 1 d post infection, the magnitude of\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    replication in the liver distinguishes abscess-susceptible and abscess-resistant strains of mice, suggesting that the immune pathways that regulate abscess formation are induced within hours. We characterized the early hepatic response with single-cell RNA sequencing and found that mice with reduced activation of early inflammatory responses, such as those lacking the LPS receptor TLR4 (Toll-like receptor 4), are resistant to abscess formation. Experiments with barcoded\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    revealed that TLR4 mediates a tradeoff between abscess formation and bacterial clearance. Together, our findings define hallmarks of\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    liver abscess formation and suggest that hyperactivation of the hepatic innate immune response drives liver abscess susceptibility.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2310053120","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T14:57:25Z","timestamp":1702565845000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["Genetic and immune determinants of\n                    <i>E. coli<\/i>\n                    liver abscess formation"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-2090","authenticated-orcid":false,"given":"Karthik","family":"Hullahalli","sequence":"first","affiliation":[{"name":"Department of Microbiology, Harvard Medical School","place":["Boston"]},{"name":"Division of Infectious Diseases, Brigham & Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7013-0932","authenticated-orcid":false,"given":"Katherine G.","family":"Dailey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Harvard Medical School","place":["Boston"]},{"name":"Division of Infectious Diseases, Brigham & Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Harvard Medical School","place":["Boston"]},{"name":"Division of Infectious Diseases, Brigham & Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Encarnacion","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical School","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Harvard Medical School","place":["Boston"]},{"name":"Division of Infectious Diseases, Brigham & Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-010X","authenticated-orcid":false,"given":"Hailong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Harvard Medical School","place":["Boston"]},{"name":"Division of Infectious Diseases, Brigham & Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-1635","authenticated-orcid":false,"given":"David W.","family":"Threadgill","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Texas A&M University","place":["College Station"]},{"name":"Department of Nutrition","place":["College Station"]},{"name":"Texas A&M University","place":["College Station"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-219X","authenticated-orcid":false,"given":"Victor M.","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical School","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-7000","authenticated-orcid":false,"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Harvard Medical School","place":["Boston"]},{"name":"Division of Infectious Diseases, Brigham & Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00355-19"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.26514"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.10.031"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01035-22"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00691-20"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00104-16"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01114-21"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78291"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz282"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00262-10"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003788"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.70910"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00887-21"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.11.030"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.614"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252529799"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065007"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-7-r82"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/71641"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnw212"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa6090"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.018"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2309151120"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0407247"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1068"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00058.2013"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0039-2018"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01448-2"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100217"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.1.118-124.2006"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055694"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000434"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.6.2980-2983.1998"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41182-020-0193-2"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000564"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01347-13"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01523-08"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2115987119"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02110-14"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03674-5"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.52"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011233"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2011.01.007"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00647"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-01947-z"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000012326"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1086\/425616"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000010628"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1502"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_5_53_2","unstructured":"K. Hullahalli Liver Single Cell RNA Sequencing at 4 hours post IV E. coli infection. Sequencing Read Archive. https:\/\/www.ncbi.nlm.nih.gov\/bioproject?term=PRJNA945406. Deposited 16 March 2023."}],"updated-by":[{"DOI":"10.1073\/pnas.2530594122","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2310053120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T18:30:22Z","timestamp":1764181822000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2310053120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,14]]},"references-count":53,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2023,12,19]]}},"alternative-id":["10.1073\/pnas.2310053120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2310053120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,14]]},"assertion":[{"value":"2023-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2310053120"}}