{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:45:28Z","timestamp":1774399528147,"version":"3.50.1"},"reference-count":86,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI140195"],"award-info":[{"award-number":["R01AI140195"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,2,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Legionella<\/jats:italic>\n              species evade degradation and proliferate within alveolar macrophages as an essential step for the manifestation of disease. However, most intracellular bacterial pathogens are restricted in neutrophils, which are the first line of innate immune defense against invading pathogens. Bacterial degradation within neutrophils is mediated by the fusion of microbicidal granules to pathogen-containing phagosomes and the generation of reactive oxygen species (ROS) by the phagocyte NADPH oxidase complex. Here, we show that human neutrophils fail to trigger microbicidal processes and, consequently, fail to restrict\n              <jats:italic>L. longbeachae<\/jats:italic>\n              . In addition, neutrophils infected with\n              <jats:italic>L. longbeachae<\/jats:italic>\n              fail to undergo a robust pro-inflammatory response, such as degranulation and IL-8 production. Here, we identify three strategies employed by\n              <jats:italic>L. longbeachae<\/jats:italic>\n              for evading restriction by neutrophils and inhibiting the neutrophil microbicidal response to other bacteria co-inhabiting in the same cell. First,\n              <jats:italic>L. longbeachae<\/jats:italic>\n              excludes the cytosolic and membrane-bound subunits of the phagocyte NADPH oxidase complex from its phagosomal membrane independent of the type 4 secretion system (T4SS). Consequently, infected neutrophils fail to generate robust ROS in response to\n              <jats:italic>L. longbeachae<\/jats:italic>\n              . Second,\n              <jats:italic>L. longbeachae<\/jats:italic>\n              impedes the fusion of azurophilic granules to its phagosome and the phagosomes of bacteria co-inhabiting the same cell through T4SS-independent mechanisms. Third,\n              <jats:italic>L. longbeachae<\/jats:italic>\n              protects phagosomes of co-inhabiting bacteria from degradation by ROS through a\n              <jats:italic>trans<\/jats:italic>\n              -acting T4SS-dependent mechanism. Collectively, we conclude that\n              <jats:italic>L. longbeachae<\/jats:italic>\n              evades restriction by human neutrophils\n              <jats:italic>via<\/jats:italic>\n              T4SS-independent mechanisms and utilizes\n              <jats:italic>trans<\/jats:italic>\n              -acting T4SS-dependent mechanisms for inhibition of neutrophil ROS generation throughout the cell cytosol.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Legionella longbeachae<\/jats:italic>\n              is commonly found in soil environments where it interacts with a wide variety of protist hosts and microbial competitors. Upon transmission to humans\n              <jats:italic>, L. longbeachae<\/jats:italic>\n              invades and replicates within alveolar macrophages, leading to the manifestation of pneumonia. In addition to alveolar macrophages, neutrophils are abundant immune cells acting as the first line of defense against invading pathogens. While most intracellular bacterial species are killed and degraded by neutrophils, we show that\n              <jats:italic>L. longbeachae<\/jats:italic>\n              evades degradation. The pathogen impairs the major neutrophils\u2019 microbicidal processes, including the fusion of microbicidal granules to the pathogen-containing vacuole. By inhibiting of assembly of the phagocyte NADPH oxidase complex, the pathogen blocks neutrophils from generating microbicide reactive oxygen species. Overall,\n              <jats:italic>L. longbeachae<\/jats:italic>\n              employs unique virulence strategies to evade the major microbicidal processes of neutrophils.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03274-24","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T14:00:16Z","timestamp":1734357616000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition and evasion of neutrophil microbicidal responses by\n            <i>Legionella longbeachae<\/i>"],"prefix":"10.1128","volume":"16","author":[{"given":"Hannah E.","family":"Hanford","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Louisville","place":["Louisville, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7459-5469","authenticated-orcid":false,"given":"Christopher T. D.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Louisville","place":["Louisville, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6171-0271","authenticated-orcid":true,"given":"Silvia","family":"Uriarte","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Louisville","place":["Louisville, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2119-2078","authenticated-orcid":true,"given":"Yousef","family":"Abu Kwaik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Louisville","place":["Louisville, USA"]},{"name":"Center for Predictive Medicine, College of Medicine, University of Louisville","place":["Louisville, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000851"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01685-14"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01140-21"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01201-20"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-09721-9"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842x(96)10041-x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10101350"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idcr.2021.e01050"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2906.221598"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000215"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.33321\/cdi.2022.46.34"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1178130"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw560"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00025-07"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00033"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.007476-0"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00461-15"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01891-14"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01313-18"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12971"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03458-20"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0281587"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.04179-22"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00208"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3481"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06124.x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00894.x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4MR0816-340R"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-90-4-496"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14911"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33230-y"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.134189"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0276460"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0047TR"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005591"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01008-21"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00373"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.10.6981"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01234.x"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005591"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00217"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2870603"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002733"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2000.61.29"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1997.4351333.x"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.3.799.bloodjournal833799"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dib.2015.12.003"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15803"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.10.5592"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-22-2880"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.11.3885.bloodjournal84113885"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci111357"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(88)90079-4"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(92)90114-4"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02013061"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12252"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.945749"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.10.3521.410k21_3521_3530"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.8.4772-4783.2004"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1209811"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1159\/000487756"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.9.5392-5401.2004"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01318-08"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evx246"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.1.208-218.2005"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0406287"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2305.161165"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep33442"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00374-19"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000273"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.ESP-0034-2018"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01272-09"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.310-321.2004"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012534"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.1.49"},{"key":"e_1_3_4_77_2","first-page":"113","article-title":"The lipopolysaccharide of Legionella pneumophila serogroup 1 (strain Philadelphia 1): chemical structure and biological significance","volume":"392","author":"Z\u00e4hringer U","year":"1995","unstructured":"Z\u00e4hringer U, Knirel YA, Lindner B, Helbig JH, Sonesson A, Marre R, Rietschel ET. 1995. The lipopolysaccharide of Legionella pneumophila serogroup 1 (strain Philadelphia 1): chemical structure and biological significance. Prog Clin Biol Res 392:113\u2013139.","journal-title":"Prog Clin Biol Res"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00301841"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiad028"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2010.01.002"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2019.102399"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.0c01669"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306219"},{"key":"e_1_3_4_84_2","first-page":"101","article-title":"Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide","volume":"119","author":"Haslett C","year":"1985","unstructured":"Haslett C, Guthrie LA, Kopaniak MM, Johnston RB Jr, Henson PM. 1985. Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. Am J Pathol 119:101\u2013110.","journal-title":"Am J Pathol"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3AB0316-139R"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-126029"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-445619"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03274-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03274-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T14:11:23Z","timestamp":1738764683000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03274-24"}},"subtitle":[],"editor":[{"given":"Victor J.","family":"Torres","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":86,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2,5]]}},"alternative-id":["10.1128\/mbio.03274-24"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03274-24","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"assertion":[{"value":"2024-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03274-24"}}