{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:43:36Z","timestamp":1781739816565,"version":"3.54.5"},"reference-count":52,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":818,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["mucosalimmunology.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Mucosal Immunology"],"published-print":{"date-parts":[[2019,11]]},"DOI":"10.1038\/s41385-019-0196-7","type":"journal-article","created":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T08:04:12Z","timestamp":1566979452000},"page":"1382-1390","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["TOLLIP deficiency is associated with increased resistance to Legionella pneumophila pneumonia"],"prefix":"10.1016","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2997-7988","authenticated-orcid":false,"given":"Javeed A.","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Emery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambasivan","family":"Venkatasubramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi F.","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Prins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Verbon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Hawn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn J.","family":"Skerrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/s41385-019-0196-7_bib1","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S1473-3099(14)70713-3","article-title":"Epidemiology and clinical management of Legionnaires' disease","volume":"14","author":"Phin","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"10.1038\/s41385-019-0196-7_bib2","first-page":"407","article-title":"Factors influencing the case-fatality rate of Legionnaires' disease","volume":"13","author":"Dominguez","year":"2009","journal-title":"Int J. Tuberc. Lung Dis."},{"key":"10.1038\/s41385-019-0196-7_bib3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0092-8674(84)90070-9","article-title":"Phagocytosis of the Legionnaires' disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil","volume":"36","author":"Horwitz","year":"1984","journal-title":"Cell"},{"key":"10.1038\/s41385-019-0196-7_bib4","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1128\/jcm.29.5.953-956.1991","article-title":"Detection of flagella in 278 Legionella strains by latex reagent sensitized with antiflagellum immunoglobulins","volume":"29","author":"Bornstein","year":"1991","journal-title":"J. Clin. Microbiol."},{"key":"10.1038\/s41385-019-0196-7_bib5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1242\/jcs.00212","article-title":"Lipopolysaccharides from Legionella and Rhizobium stimulate mouse bone marrow granulocytes via Toll-like receptor 2","volume":"116","author":"Girard","year":"2003","journal-title":"J. Cell Sci."},{"key":"10.1038\/s41385-019-0196-7_bib6","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-micro-102215-095557","article-title":"Autophagy evasion and endoplasmic reticulum saubversion: the Yin and Yang of legionella intracellularinfection","volume":"70","author":"Sherwood","year":"2016","journal-title":"Annu. Rev. Microbiol."},{"key":"10.1038\/s41385-019-0196-7_bib7","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1128\/IAI.01382-05","article-title":"Membrane vesicles shed by Legionella pneumophila inhibit fusion of phagosomes with lysosomes","volume":"74","author":"Fernandez-Moreira","year":"2006","journal-title":"Infect. Immun."},{"key":"10.1038\/s41385-019-0196-7_bib8","doi-asserted-by":"crossref","first-page":"E6790","DOI":"10.1073\/pnas.1508716112","article-title":"Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response","volume":"112","author":"Hempstead","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1038\/s41385-019-0196-7_bib9","doi-asserted-by":"crossref","first-page":"e1005591","DOI":"10.1371\/journal.ppat.1005591","article-title":"Neutrophil and alveolar macrophage-mediated innate immune control of Legionella pneumophila lung infection via TNF and ROS","volume":"12","author":"Ziltener","year":"2016","journal-title":"PLoS Pathog."},{"key":"10.1038\/s41385-019-0196-7_bib10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jiac.2016.09.010","article-title":"TNF-alpha inhibits the growth of Legionella pneumophila in airway epithelial cells by inducing apoptosis","volume":"23","author":"Kawamoto","year":"2017","journal-title":"J. Infect. Chemother."},{"key":"10.1038\/s41385-019-0196-7_bib11","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1128\/IAI.73.1.352-361.2005","article-title":"Differential roles of Toll-like receptors 2 and 4 in in vitro responses of macrophages to Legionella pneumophila","volume":"73","author":"Akamine","year":"2005","journal-title":"Infect. Immun."},{"key":"10.1038\/s41385-019-0196-7_bib12","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1084\/jem.20051659","article-title":"Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection","volume":"203","author":"Molofsky","year":"2006","journal-title":"J. Exp. Med."},{"key":"10.1038\/s41385-019-0196-7_bib13","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/ni1305","article-title":"The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection","volume":"7","author":"Zamboni","year":"2006","journal-title":"Nat. Immunol."},{"key":"10.1038\/s41385-019-0196-7_bib14","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.4049\/jimmunol.179.10.6981","article-title":"Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila","volume":"179","author":"Hawn","year":"2007","journal-title":"J. Immunol."},{"key":"10.1038\/s41385-019-0196-7_bib15","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/nature10510","article-title":"The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus","volume":"477","author":"Zhao","year":"2011","journal-title":"Nature"},{"key":"10.1038\/s41385-019-0196-7_bib16","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/35014038","article-title":"Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor","volume":"2","author":"Burns","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"10.1038\/s41385-019-0196-7_bib17","doi-asserted-by":"crossref","first-page":"7059","DOI":"10.1074\/jbc.M109537200","article-title":"Negative Regulation of Toll-like Receptor-mediated Signaling by Tollip","volume":"277","author":"Zhang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1038\/s41385-019-0196-7_bib18","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cell.2014.05.048","article-title":"Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family","volume":"158","author":"Lu","year":"2014","journal-title":"Cell"},{"key":"10.1038\/s41385-019-0196-7_bib19","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.cell.2016.05.078","article-title":"An ER-associated pathway defines endosomal architecture for controlled cargo transport","volume":"166","author":"Jongsma","year":"2016","journal-title":"Cell"},{"key":"10.1038\/s41385-019-0196-7_bib20","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.4049\/jimmunol.1103541","article-title":"Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis","volume":"189","author":"Shah","year":"2012","journal-title":"J. Immunol."},{"key":"10.1038\/s41385-019-0196-7_bib21","doi-asserted-by":"crossref","first-page":"e0003875","DOI":"10.1371\/journal.pntd.0003875","article-title":"Polymorphisms in the TOLLIP gene influence susceptibility to cutaneous Leishmaniasis caused by Leishmania guyanensis in the Amazonas State of Brazil","volume":"9","author":"Araujo","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1038\/s41385-019-0196-7_bib22","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/infdis\/jiv570","article-title":"Genetic variation in toll-interacting protein is associated with leprosy susceptibility and cutaneous expression of interleukin 1 receptor antagonist","volume":"213","author":"Shah","year":"2016","journal-title":"J. Infect. Dis."},{"key":"10.1038\/s41385-019-0196-7_bib23","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1146\/annurev-genom-091212-153448","article-title":"The genetic theory of infectious diseases: a brief history and selected illustrations","volume":"14","author":"Casanova","year":"2013","journal-title":"Annu Rev. Genomics. Hum. Genet."},{"key":"10.1038\/s41385-019-0196-7_bib24","doi-asserted-by":"crossref","first-page":"e1006829","DOI":"10.1371\/journal.ppat.1006829","article-title":"The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires' disease in humans","volume":"14","author":"Ruiz-Moreno","year":"2018","journal-title":"PLoS Pathog."},{"key":"10.1038\/s41385-019-0196-7_bib25","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1084\/jem.20031220","article-title":"A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease","volume":"198","author":"Hawn","year":"2003","journal-title":"J. Exp. Med."},{"key":"10.1038\/s41385-019-0196-7_bib26","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1164\/rccm.201611-2346OC","article-title":"A functional TOLLIP variant is associated with BCG-specific immune responses and tuberculosis","volume":"196","author":"Shah","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1038\/s41385-019-0196-7_bib27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3201\/eid0801.010176","article-title":"A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999","volume":"8","author":"Den Boer","year":"2002","journal-title":"Emerg. Infect. Dis."},{"key":"10.1038\/s41385-019-0196-7_bib28","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/cid\/cir378","article-title":"Racial differences in tuberculosis infection in United States communities: the coronary artery risk development in young adults study","volume":"53","author":"Nahid","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"10.1038\/s41385-019-0196-7_bib29","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1128\/jcm.22.6.1040-1044.1985","article-title":"Method for the isolation of highly purified Salmonella flagellins","volume":"22","author":"Ibrahim","year":"1985","journal-title":"J. Clin. Microbiol."},{"key":"10.1038\/s41385-019-0196-7_bib30","first-page":"11","article-title":"[Biological diagnosis of Legionnaire's disease]","volume":"1","author":"Edelstein","year":"1984","journal-title":"Rev. Mal. Respir."},{"key":"10.1038\/s41385-019-0196-7_bib31","doi-asserted-by":"crossref","first-page":"e64129","DOI":"10.1371\/journal.pone.0064129","article-title":"Phylogenetic reconstruction of the Legionella pneumophila Philadelphia-1 laboratory strains through comparative genomics","volume":"8","author":"Rao","year":"2013","journal-title":"PLoS One"},{"key":"10.1038\/s41385-019-0196-7_bib32","doi-asserted-by":"crossref","first-page":"e1004704","DOI":"10.1371\/journal.ppat.1004704","article-title":"Sensing cytosolic RpsL by macrophages induces lysosomal cell death and termination of bacterial infection","volume":"11","author":"Zhu","year":"2015","journal-title":"PLoS Pathog"},{"key":"10.1038\/s41385-019-0196-7_bib33","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1128\/MCB.26.3.735-742.2006","article-title":"Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide","volume":"26","author":"Didierlaurent","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"10.1038\/s41385-019-0196-7_bib34","doi-asserted-by":"crossref","DOI":"10.1186\/s12864-015-2022-2","article-title":"Prior infection with Type A Francisella tularensis antagonizes the pulmonary transcriptional response to an aerosolized Toll-like receptor 4 agonist","volume":"16","author":"Walters","year":"2015","journal-title":"BMC Genomics"},{"key":"10.1038\/s41385-019-0196-7_bib35","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.1128\/IAI.01891-14","article-title":"Alveolar macrophages and neutrophils are the primary reservoirs for Legionella pneumophila and mediate cytosolic surveillance of type IV secretion","volume":"82","author":"Copenhaver","year":"2014","journal-title":"Infect. Immun."},{"key":"10.1038\/s41385-019-0196-7_bib36","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/ni1362","article-title":"Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells","volume":"7","author":"Uematsu","year":"2006","journal-title":"Nat. Immunol."},{"key":"10.1038\/s41385-019-0196-7_bib37","doi-asserted-by":"crossref","first-page":"e1001289","DOI":"10.1371\/journal.ppat.1001289","article-title":"Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila","volume":"7","author":"Fontana","year":"2011","journal-title":"PLoS Pathog"},{"key":"10.1038\/s41385-019-0196-7_bib38","doi-asserted-by":"crossref","first-page":"6808","DOI":"10.4049\/jimmunol.180.10.6808","article-title":"NAIP and Ipaf control Legionella pneumophila replication in human cells","volume":"180","author":"Vinzing","year":"2008","journal-title":"J. Immunol."},{"key":"10.1038\/s41385-019-0196-7_bib39","doi-asserted-by":"crossref","first-page":"e004078","DOI":"10.1161\/JAHA.116.004078","article-title":"Tollip deficiency alters atherosclerosis and steatosis by disrupting lipophagy","volume":"6","author":"Chen","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"10.1038\/s41385-019-0196-7_bib40","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nri3532","article-title":"Autophagy in infection, inflammation and immunity","volume":"13","author":"Deretic","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"10.1038\/s41385-019-0196-7_bib41","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1172\/JCI73945","article-title":"Immunologic manifestations of autophagy","volume":"125","author":"Deretic","year":"2015","journal-title":"J. Clin. Invest"},{"key":"10.1038\/s41385-019-0196-7_bib42","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1600-065X.2011.01037.x","article-title":"Two signal models in innate immunity","volume":"243","author":"Fontana","year":"2011","journal-title":"Immunol. Rev."},{"key":"10.1038\/s41385-019-0196-7_bib43","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nature07383","article-title":"Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production","volume":"456","author":"Saitoh","year":"2008","journal-title":"Nature"},{"key":"10.1038\/s41385-019-0196-7_bib44","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.ajpath.2015.12.026","article-title":"An essential role for SHARPIN in the regulation of caspase 1 activity in sepsis","volume":"186","author":"Nastase","year":"2016","journal-title":"Am. J. Pathol."},{"key":"10.1038\/s41385-019-0196-7_bib45","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1080\/15548627.2016.1166325","article-title":"Legionella pneumophila restrains autophagy by modulating the host's sphingolipid metabolism","volume":"12","author":"Rolando","year":"2016","journal-title":"Autophagy"},{"key":"10.1038\/s41385-019-0196-7_bib46","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/ni.1980","article-title":"Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome","volume":"12","author":"Nakahira","year":"2011","journal-title":"Nat. Immunol."},{"key":"10.1038\/s41385-019-0196-7_bib47","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0006-291X(03)01049-0","article-title":"Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock","volume":"306","author":"Sakaguchi","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1038\/s41385-019-0196-7_bib48","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature07203","article-title":"From endoplasmic-reticulum stress to the inflammatory response","volume":"454","author":"Zhang","year":"2008","journal-title":"Nature"},{"key":"10.1038\/s41385-019-0196-7_bib49","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0140-6736(05)67424-7","article-title":"Genetic association studies","volume":"366","author":"Cordell","year":"2005","journal-title":"Lancet"},{"key":"10.1038\/s41385-019-0196-7_bib50","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1128\/JCM.40.4.1352-1362.2002","article-title":"Genetic and phenotypic differences between Legionella pneumophila strains","volume":"40","author":"Samrakandi","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"10.1038\/s41385-019-0196-7_bib51","doi-asserted-by":"crossref","first-page":"E10446","DOI":"10.1073\/pnas.1708553114","article-title":"Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries","volume":"114","author":"Shames","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1038\/s41385-019-0196-7_bib52","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/ng.3481","article-title":"Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires","volume":"48","author":"Burstein","year":"2016","journal-title":"Nat. Genet."}],"container-title":["Mucosal Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41385-019-0196-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41385-019-0196-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1933021922004585?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1933021922004585?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41385-019-0196-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:13:54Z","timestamp":1761830034000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1933021922004585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["S1933021922004585"],"URL":"https:\/\/doi.org\/10.1038\/s41385-019-0196-7","relation":{},"ISSN":["1933-0219"],"issn-type":[{"value":"1933-0219","type":"print"}],"subject":[],"published":{"date-parts":[[2019,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TOLLIP deficiency is associated with increased resistance to Legionella pneumophila pneumonia","name":"articletitle","label":"Article Title"},{"value":"Mucosal Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/s41385-019-0196-7","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2019 \u00a9 Society for Mucosal Immunology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}