{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:05:38Z","timestamp":1791990338568,"version":"4.4.0"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Buruli ulcer (BU), caused by<jats:italic>Mycobacterium ulcerans<\/jats:italic>, is a devastating necrotizing skin disease. Key to its pathogenesis is mycolactone, the exotoxin virulence factor that is both immunosuppressive and cytotoxic. The discovery that the essential Sec61 translocon is the major cellular target of mycolactone explains much of the disease pathology, including the immune blockade. Sec61 inhibition leads to a loss in production of nearly all cytokines from monocytes, macrophages, dendritic cells and T cells, as well as antigen presentation pathway proteins and costimulatory molecules. However, there has long been evidence that the immune system is not completely incapable of responding to<jats:italic>M. ulcerans<\/jats:italic>infection. In particular, IL-1\u03b2 was recently shown to be present in BU lesions, and to be induced from<jats:italic>M. ulcerans<\/jats:italic>-exposed macrophages in a mycolactone-dependent manner. This has important implications for our understanding of BU, showing that mycolactone can act as the \u201csecond signal\u201d for IL-1\u03b2 production without inhibiting the pathways of unconventional secretion it uses for cellular release. In this Perspective article, we validate and discuss this recent advance, which is entirely in-line with our understanding of mycolactone\u2019s inhibition of the Sec61 translocon. However, we also show that the IL-1 receptor, which uses the conventional secretory pathway, is sensitive to mycolactone blockade at Sec61. Hence, a more complete understanding of the mechanisms regulating IL-1\u03b2 function in skin tissue, including the transient intra-macrophage stage of<jats:italic>M. ulcerans<\/jats:italic>infection, is urgently needed to uncover the double-edged sword of IL-1\u03b2 in BU pathogenesis, treatment and wound healing.<\/jats:p>","DOI":"10.3389\/fimmu.2021.788146","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T05:49:18Z","timestamp":1643176158000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["The One That Got Away: How Macrophage-Derived IL-1\u03b2 Escapes the Mycolactone-Dependent Sec61 Blockade in Buruli Ulcer"],"prefix":"10.3389","volume":"12","author":[{"given":"Belinda S.","family":"Hall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise Tzung-Harn","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sacre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Simmonds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s40475-018-0166-2","article-title":"Buruli Ulcer: A Review of the Current Knowledge","volume":"5","author":"Yotsu","year":"2018","journal-title":"Curr Trop Med Rep"},{"key":"B2","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3201\/eid2401.171070","article-title":"Increased Severity and Spread of Mycobacterium Ulcerans, Southeastern Australia","volume":"24","author":"Tai","year":"2018","journal-title":"Emerging Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30171-8","article-title":"Mapping the Global Distribution of Buruli Ulcer: A Systematic Review With Evidence Consensus","volume":"7","author":"Simpson","year":"2019","journal-title":"Lancet Glob Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30047-7","article-title":"Rifampicin and Clarithromycin (Extended Release) Versus Rifampicin and Streptomycin for Limited Buruli Ulcer Lesions: A Randomised, Open-Label, Non-Inferiority Phase 3 Trial","volume":"395","author":"Phillips","year":"2020","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30478-5","article-title":"Buruli Ulcer: Cured by 8 Weeks of Oral Antibiotics","volume":"395","author":"Johnson","year":"2020","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5403.854","article-title":"Mycolactone: A Polyketide Toxin From Mycobacterium Ulcerans Required for Virulence","volume":"283","author":"George","year":"1999","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305877101","article-title":"Giant Plasmid-Encoded Polyketide Synthases Produce the Macrolide Toxin of Mycobacterium Ulcerans","volume":"101","author":"Stinear","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e70520","DOI":"10.1371\/journal.pone.0070520","article-title":"The Cell Wall-Associated Mycolactone Polyketide Synthases are Necessary But Not Sufficient for Mycolactone Biosynthesis","volume":"8","author":"Porter","year":"2013","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1101\/gr.5942807","article-title":"Reductive Evolution and Niche Adaptation Inferred From the Genome of Mycobacterium Ulcerans, the Causative Agent of Buruli Ulcer","volume":"17","author":"Stinear","year":"2007","journal-title":"Genome Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nrmicro2077","article-title":"Buruli Ulcer: Reductive Evolution Enhances Pathogenicity of Mycobacterium Ulcerans","volume":"7","author":"Demangel","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e1005011","DOI":"10.1371\/journal.ppat.1005011","article-title":"Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin is Strongly Associated With Fibrin Deposition in Buruli Ulcer Lesions","volume":"11","author":"Ogbechi","year":"2015","journal-title":"PloS Pathog"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1101\/2021.08.04.21261598","article-title":"Aberrant Stromal Tissue Factor and Mycolactone-Driven Vascular Permeability, Exacerbated by IL-1\u03b2, Orchestrate Pathogenic Fibrin Formation in Buruli Ulcer Lesions","author":"Hsieh","year":"2021","journal-title":"medRxiv"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070234","article-title":"Selective Suppression of Dendritic Cell Functions by Mycobacterium Ulcerans Toxin Mycolactone","volume":"204","author":"Coutanceau","year":"2007","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.163.7.3928","article-title":"The Inhibitory Action of Mycobacterium Ulcerans Soluble Factor on Monocyte\/T Cell Cytokine Production and NF-Kappa B Function","volume":"163","author":"Pahlevan","year":"1999","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802294","article-title":"Mycolactone Inhibits Monocyte Cytokine Production by a Posttranscriptional Mechanism","volume":"182","author":"Simmonds","year":"2009","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1004061","DOI":"10.1371\/journal.ppat.1004061","article-title":"The Pathogenic Mechanism of the Mycobacterium Ulcerans Virulence Factor, Mycolactone, Depends on Blockade of Protein Translocation Into the ER","volume":"10","author":"Hall","year":"2014","journal-title":"PloS Pathog"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902854","article-title":"Mycolactone Suppresses T Cell Responsiveness by Altering Both Early Signaling and Posttranslational Events","volume":"184","author":"Boulkroun","year":"2010","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160662","article-title":"Mycolactone Subverts Immunity by Selectively Blocking the Sec61 Translocon","volume":"213","author":"Baron","year":"2016","journal-title":"J Exp Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00290-07","article-title":"Mycolactone-Mediated Inhibition of Tumor Necrosis Factor Production by Macrophages Infected With Mycobacterium Ulcerans has Implications for the Control of Infection","volume":"75","author":"Torrado","year":"2007","journal-title":"Infect Immun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016496108","article-title":"Mycolactone Impairs T Cell Homing by Suppressing microRNA Control of L-Selectin Expression","volume":"108","author":"Guenin-Mace","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66576","article-title":"Mycolactone Activation of Wiskott-Aldrich Syndrome Proteins Underpins Buruli Ulcer Formation","volume":"123","author":"Guenin-Mace","year":"2013","journal-title":"J Clin Invest"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20210345","article-title":"Mycolactone Enhances the Ca2+ Leak From Endoplasmic Reticulum by Trapping Sec61 Translocons in a Ca2+ Permeable State","volume":"478","author":"Bhadra","year":"2021","journal-title":"Biochem J"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e0008709","DOI":"10.1371\/journal.pntd.0008709","article-title":"Mycolactone Induces Cell Death by SETD1B-Dependent Degradation of Glutathione","volume":"14","author":"F\u00f6rster","year":"2020","journal-title":"PloS Negl Trop Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1177\/15353702211015628","article-title":"Natural Antioxidants Attenuate Mycolactone Toxicity to RAW 264.7 Macrophages","volume":"246","author":"Kwaffo","year":"2021","journal-title":"Exp Biol Med (Maywood)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e13839","DOI":"10.1371\/journal.pone.0013839","article-title":"Antioxidants Protect Keratinocytes Against M. Ulcerans Mycolactone Cytotoxicity","volume":"5","author":"Gronberg","year":"2010","journal-title":"PloS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41419-018-0427-y","article-title":"Inhibition of Sec61-Dependent Translocation by Mycolactone Uncouples the Integrated Stress Response From ER Stress, Driving Cytotoxicity via Translational Activation of ATF4","volume":"9","author":"Ogbechi","year":"2018","journal-title":"Cell Death Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA118.000824","article-title":"Proteomics Reveals Scope of Mycolactone-Mediated Sec61 Blockade and Distinctive Stress Signature","volume":"17","author":"Morel","year":"2018","journal-title":"Mol Cell Proteomics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2021.1961067","article-title":"Inhibition of the SEC61 Translocon by Mycolactone Induces a Protective Autophagic Response Controlled by EIF2S1-Dependent Translation That Does Not Require ULK1 Activity","author":"Hall","year":"2021","journal-title":"Autophagy"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e3066","DOI":"10.1371\/journal.pntd.0003066","article-title":"Proteomic Analysis of the Action of the Mycobacterium Ulcerans Toxin Mycolactone: Targeting Host Cells Cytoskeleton and Collagen","volume":"8","author":"Gama","year":"2014","journal-title":"PloS Negl Trop Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00053","article-title":"The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer Through Inhibition of mTOR","volume":"12","author":"Bieri","year":"2017","journal-title":"ACS Chem Biol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.877-883.2000","article-title":"A Mycobacterium Ulcerans Toxin, Mycolactone, Causes Apoptosis in Guinea Pig Ulcers and Tissue Culture Cells","volume":"68","author":"George","year":"2000","journal-title":"Infection Immun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00557.x","article-title":"Mycobacterium Ulcerans Toxic Macrolide, Mycolactone Modulates the Host Immune Response and Cellular Location of M. Ulcerans In Vitro and In Vivo","volume":"7","author":"Adusumilli","year":"2005","journal-title":"Cell Microbiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0004678","DOI":"10.1371\/journal.pntd.0004678","article-title":"Local Cellular Immune Responses and Pathogenesis of Buruli Ulcer Lesions in the Experimental Mycobacterium Ulcerans Pig Infection Model","volume":"10","author":"Bolz","year":"2016","journal-title":"PloS Negl Trop Dis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e2968","DOI":"10.1371\/journal.pntd.0002968","article-title":"Experimental Infection of the Pig With Mycobacterium Ulcerans: A Novel Model for Studying the Pathogenesis of Buruli Ulcer Disease","volume":"8","author":"Bolz","year":"2014","journal-title":"PloS Negl Trop Dis"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050375","article-title":"Nerve Damage in Mycobacterium Ulcerans-Infected Mice: Probable Cause of Painlessness in Buruli Ulcer","volume":"168","author":"Goto","year":"2006","journal-title":"Am J Pathol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01588-07","article-title":"Mycolactone is Responsible for the Painlessness of Mycobacterium Ulcerans Infection (Buruli Ulcer) in a Murine Study","volume":"76","author":"En","year":"2008","journal-title":"Infect Immun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.040","article-title":"Mycobacterial Toxin Induces Analgesia in Buruli Ulcer by Targeting the Angiotensin Pathways","volume":"157","author":"Marion","year":"2014","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.182352","article-title":"Mechanistic Insights Into the Inhibition of Sec61-Dependent Co- and Post-Translational Translocation by Mycolactone","volume":"129","author":"McKenna","year":"2016","journal-title":"J Cell Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b13506","article-title":"Ipomoeassin F Binds Sec61\u03b1 to Inhibit Protein Translocation","volume":"141","author":"Zong","year":"2019","journal-title":"J Am Chem Soc"},{"key":"B40","volume-title":"WHO Meeting on Buruli Ulcer and Other Skin NTDs. Final Report","year":"2019"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e0009678","DOI":"10.1371\/journal.pntd.0009678","article-title":"Understanding the Transmission of Mycobacterium Ulcerans: A Step Towards Controlling Buruli Ulcer","volume":"15","author":"Muleta","year":"2021","journal-title":"PloS Negl Trop Dis"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuab045","article-title":"A Need for Null Models in Understanding Disease Transmission: The Example of Mycobacterium Ulcerans (Buruli Ulcer Disease)","author":"Receveur","year":"2021","journal-title":"FEMS Microbiol Rev"},{"key":"B43","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.molcel.2020.06.013","article-title":"Structure of the Inhibited State of the Sec Translocon","volume":"79","author":"G\u00e9rard","year":"2020","journal-title":"Mol Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.198655","article-title":"Mycolactone Reveals the Substrate-Driven Complexity of Sec61-Dependent Transmembrane Protein Biogenesis","volume":"130","author":"McKenna","year":"2017","journal-title":"J Cell Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2743-2","article-title":"Inhibitors of Protein Translocation Across Membranes of the Secretory Pathway: Novel Antimicrobial and Anticancer Agents","volume":"75","author":"Van Puyenbroeck","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/boc.201800030","article-title":"Sec61 Blockade by Mycolactone: A Central Mechanism in Buruli Ulcer Disease","volume":"110","author":"Demangel","year":"2018","journal-title":"Biol Cell"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705242114","article-title":"Sec61 Blockade by Mycolactone Inhibits Antigen Cross-Presentation Independently of Endosome-to-Cytosol Export","volume":"114","author":"Grotzke","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e0005415","DOI":"10.1371\/journal.pntd.0005415","article-title":"Analysis of Mycobacterium Ulcerans-Specific T-Cell Cytokines for Diagnosis of Buruli Ulcer Disease and as Potential Indicator for Disease Progression","volume":"11","author":"Nausch","year":"2017","journal-title":"PloS Negl Trop Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.3.1704-1707.2001","article-title":"Immune Response to Infection With Mycobacterium Ulcerans","volume":"69","author":"Gooding","year":"2001","journal-title":"Infection Immun"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1086\/368315","article-title":"Acquired T-Helper 1 Lymphocyte Anergy Following Infection With Mycobacterium Ulcerans","volume":"36","author":"Gooding","year":"2003","journal-title":"Clin Infect Dis an Off Publ Infect Dis Soc America"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1086\/646615","article-title":"Immunosuppressive Signature of Cutaneous Mycobacterium Ulcerans Infection in the Peripheral Blood of Patients With Buruli Ulcer Disease","volume":"200","author":"Phillips","year":"2009","journal-title":"J Infect Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e5294","DOI":"10.7717\/peerj.5294","article-title":"IFN-\u03b3 and IL-5 Whole Blood Response Directed Against Mycolactone Polyketide Synthase Domains in Patients With Mycobacterium Ulcerans Infection","volume":"6","author":"Loglo","year":"2018","journal-title":"PeerJ"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5562-5567.2002","article-title":"Cytokine Profiles of Patients Infected With Mycobacterium Ulcerans and Unaffected Household Contacts","volume":"70","author":"Gooding","year":"2002","journal-title":"Infection Immun"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3201\/eid0906.020485","article-title":"Histopathologic Features of Mycobacterium Ulcerans Infection","volume":"9","author":"Guarner","year":"2003","journal-title":"Emerging Infect Dis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e1747","DOI":"10.1371\/journal.pntd.0001747","article-title":"Spontaneous Clearance of a Secondary Buruli Ulcer Lesion Emerging Ten Months After Completion of Chemotherapy\u2013a Case Report From Togo","volume":"6","author":"Beissner","year":"2012","journal-title":"PloS Negl Trop Dis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"e1290","DOI":"10.1371\/journal.pntd.0001290","article-title":"Spontaneous Clearance of Mycobacterium Ulcerans in a Case of Buruli Ulcer","volume":"5","author":"Gordon","year":"2011","journal-title":"PloS Negl Trop Dis"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e0007178","DOI":"10.1371\/journal.pntd.0007178","article-title":"Spontaneous Healing of Mycobacterium Ulcerans Disease in Australian Patients","volume":"13","author":"O'Brien","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B58","doi-asserted-by":"publisher","first-page":"e0004265","DOI":"10.1371\/journal.pntd.0004265","article-title":"Spontaneous Healing of Mycobacterium Ulcerans Lesions in the Guinea Pig Model","volume":"9","author":"Silva-Gomes","year":"2015","journal-title":"PloS Negl Trop Dis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502194","article-title":"FVB\/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium Ulcerans and Switch M. Ulcerans Into a Low Mycolactone Producer","volume":"196","author":"Marion","year":"2016","journal-title":"J Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"eaax7781","DOI":"10.1126\/sciadv.aax7781","article-title":"Skin-Specific Antibodies Neutralizing Mycolactone Toxin During the Spontaneous Healing of Mycobacterium Ulcerans Infection","volume":"6","author":"Foulon","year":"2020","journal-title":"Sci Adv"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2021.1929749","article-title":"Transcriptional Adaptation of Mycobacterium Ulcerans in an Original Mouse Model: New Insights Into the Regulation of Mycolactone","volume":"12","author":"Robbe-Saule","year":"2021","journal-title":"Virulence"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e0004671","DOI":"10.1371\/journal.pntd.0004671","article-title":"Genetic Variation in Autophagy-Related Genes Influences the Risk and Phenotype of Buruli Ulcer","volume":"10","author":"Capela","year":"2016","journal-title":"PloS Negl Trop Dis"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364281","article-title":"Susceptibility to Buruli Ulcer is Associated With the SLC11A1 (NRAMP1) D543N Polymorphism","volume":"7","author":"Stienstra","year":"2006","journal-title":"Genes Immun"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.3389\/fmicb.2017.01903","article-title":"Susceptibility to Mycobacterium Ulcerans Disease (Buruli Ulcer) Is Associated With IFNG and iNOS Gene Polymorphisms","volume":"8","author":"Bibert","year":"2017","journal-title":"Front Microbiol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/s42003-020-0920-6","article-title":"Genome-Wide Association Study of Buruli Ulcer in Rural Benin Highlights Role of Two LncRNAs and the Autophagy Pathway","volume":"3","author":"Manry","year":"2020","journal-title":"Commun Biol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e1009107","DOI":"10.1371\/journal.ppat.1009107","article-title":"Mycolactone Toxin Induces an Inflammatory Response by Targeting the IL-1\u03b2 Pathway: Mechanistic Insight Into Buruli Ulcer Pathophysiology","volume":"16","author":"Foulon","year":"2020","journal-title":"PloS Pathog"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/0896-8411(89)90129-7","article-title":"Cytokine Production in Culture by Cells Isolated From the Synovial Membrane","volume":"2","author":"Brennan","year":"1989","journal-title":"J Autoimmun"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546123","article-title":"Oligodeoxynucleotide Inhibition of Toll-Like Receptors 3, 7, 8, and 9 Suppresses Cytokine Production in a Human Rheumatoid Arthritis Model","volume":"46","author":"Sacre","year":"2016","journal-title":"Eur J Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.4.2148","article-title":"Selective Use of TRAM in Lipopolysaccharide (LPS) and Lipoteichoic Acid (LTA) Induced NF-kappaB Activation and Cytokine Production in Primary Human Cells: TRAM is an Adaptor for LPS and LTA Signaling","volume":"178","author":"Sacre","year":"2007","journal-title":"J Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa220","article-title":"TLR1\/2 and 5 Induce Elevated Cytokine Levels From Rheumatoid Arthritis Monocytes Independent of ACPA or RF Autoantibody Status","volume":"59","author":"Thwaites","year":"2020","journal-title":"Rheumatol (Oxford)"},{"key":"B71","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1146\/annurev.immunol.14.1.397","article-title":"Role of Cytokines in Rheumatoid Arthritis","volume":"14","author":"Feldmann","year":"1996","journal-title":"Annu Rev Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep293","article-title":"Investigating the Role of the Interleukin-23\/-17A Axis in Rheumatoid Arthritis","volume":"48","author":"Hillyer","year":"2009","journal-title":"Rheumatol (Oxford)"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1002\/art.38055","article-title":"Selective Blockade of Tumor Necrosis Factor Receptor I Inhibits Proinflammatory Cytokine and Chemokine Production in Human Rheumatoid Arthritis Synovial Membrane Cell Cultures","volume":"65","author":"Schmidt","year":"2013","journal-title":"Arthritis Rheum"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060657","article-title":"The Toll-Like Receptor Adaptor Proteins MyD88 and Mal\/TIRAP Contribute to the Inflammatory and Destructive Processes in a Human Model of Rheumatoid Arthritis","volume":"170","author":"Sacre","year":"2007","journal-title":"Am J Pathol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.8002","article-title":"Inhibitors of TLR8 Reduce TNF Production From Human Rheumatoid Synovial Membrane Cultures","volume":"181","author":"Sacre","year":"2008","journal-title":"J Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5668","article-title":"Defining Therapeutic Targets by Using Adenovirus: Blocking NF-kappaB Inhibits Both Inflammatory and Destructive Mechanisms in Rheumatoid Synovium But Spares Anti-Inflammatory Mediators","volume":"96","author":"Bondeson","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.3389\/fimmu.2019.01412","article-title":"Structural Basis of IL-1 Family Cytokine Signaling","volume":"10","author":"Fields","year":"2019","journal-title":"Front Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"e62","DOI":"10.1371\/journal.ppat.0030062","article-title":"Impact of Mycobacterium Ulcerans Biofilm on Transmissibility to Ecological Niches and Buruli Ulcer Pathogenesis","volume":"3","author":"Marsollier","year":"2007","journal-title":"PloS Pathog"},{"key":"B79","doi-asserted-by":"publisher","first-page":"e0006058","DOI":"10.1371\/journal.pntd.0006058","article-title":"Mycolactone Displays Anti-Inflammatory Effects on the Nervous System","volume":"11","author":"Isaac","year":"2017","journal-title":"PloS Negl Trop Dis"},{"key":"B80","doi-asserted-by":"publisher","first-page":"e1000661","DOI":"10.1371\/journal.ppat.1000661","article-title":"IL-1\u03b2 Processing in Host Defense: Beyond the Inflammasomes","volume":"6","author":"Netea","year":"2010","journal-title":"PloS Pathog"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2237","article-title":"Regulation of Inflammasome Signaling","volume":"13","author":"Rathinam","year":"2012","journal-title":"Nat Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S288547","article-title":"Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology","volume":"10","author":"Unterberger","year":"2021","journal-title":"Immunotargets Ther"},{"key":"B83","doi-asserted-by":"publisher","first-page":"jcs250449","DOI":"10.1242\/jcs.250449","article-title":"FGF2 and IL-1\u03b2 - Explorers of Unconventional Secretory Pathways at a Glance","volume":"133","author":"Pallotta","year":"2020","journal-title":"J Cell Sci"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/nature18629","article-title":"Inflammasome-Activated Gasdermin D Causes Pyroptosis by Forming Membrane Pores","volume":"535","author":"Liu","year":"2016","journal-title":"Nature"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03478-3","article-title":"Gasdermin D Pore Structure Reveals Preferential Release of Mature Interleukin-1","volume":"593","author":"Xia","year":"2021","journal-title":"Nature"},{"key":"B86","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.cell.2020.03.031","article-title":"A Translocation Pathway for Vesicle-Mediated Unconventional Protein Secretion","volume":"181","author":"Zhang","year":"2020","journal-title":"Cell"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2017.00077","article-title":"Inflammasome and Autophagy Regulation - a Two-Way Street","volume":"23","author":"Sun","year":"2017","journal-title":"Mol Med"},{"key":"B88","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 Family in Innate Inflammation and Acquired Immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol Rev"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/path.4116","article-title":"Inflammasomes in Wound Healing and Fibrosis","volume":"229","author":"Artlett","year":"2013","journal-title":"J Pathol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"665","DOI":"10.3390\/life11070665","article-title":"Cutaneous Wound Healing: An Update From Physiopathology to Current Therapies","volume":"11","author":"Gushiken","year":"2021","journal-title":"Life (Basel)"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.3389\/fimmu.2019.01426","article-title":"IL-1 Family Cytokine Regulation of Vascular Permeability and Angiogenesis","volume":"10","author":"Fahey","year":"2019","journal-title":"Front Immunol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1189\/jlb.0113035","article-title":"Mouse Neutrophils Express the Decoy Type 2 Interleukin-1 Receptor (IL-1R2) Constitutively and in Acute Inflammatory Conditions","volume":"94","author":"Martin","year":"2013","journal-title":"J Leukoc Biol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.587929","article-title":"Role of Interleukin-1 Family Members and Signaling Pathways in KSHV Pathogenesis","volume":"10","author":"Barrett","year":"2020","journal-title":"Front Cell infection Microbiol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41598-018-19248-7","article-title":"Salient Type 1 Interleukin 1 Receptor Expression in Peripheral non-Immune Cells","volume":"8","author":"Song","year":"2018","journal-title":"Sci Rep"},{"key":"B95","doi-asserted-by":"publisher","first-page":"iii2","DOI":"10.1093\/rheumatology\/keh201","article-title":"The Role of Interleukin-1 in the Pathogenesis of Rheumatoid Arthritis","volume":"43","author":"Kay","year":"2004","journal-title":"Rheumatol (Oxford)"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1080\/03009740600938647","article-title":"Non-Complementaemic Urticarial Vasculitis: Successful Treatment With the IL-1 Receptor Antagonist, Anakinra","volume":"36","author":"Botsios","year":"2007","journal-title":"Scand J Rheumatol"},{"key":"B97","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.jaci.2013.04.008","article-title":"Efficacy and Safety of Canakinumab in Urticarial Vasculitis: An Open-Label Study","volume":"132","author":"Krause","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199807000-00011","article-title":"Topical Modulation of Interleukin-1 Activity in Corneal Neovascularization","volume":"17","author":"Dana","year":"1998","journal-title":"Cornea"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1450","article-title":"Blocking Interleukin-1\u03b2 Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes","volume":"62","author":"Mirza","year":"2013","journal-title":"Diabetes"},{"key":"B100","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13075-017-1222-3","article-title":"Treatment of Mucocutaneous Manifestations in Beh\u00e7et's Disease With Anakinra: A Pilot Open-Label Study","volume":"19","author":"Grayson","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.008557","article-title":"Interleukin-1 Receptor Antagonist is Beneficial After Subarachnoid Haemorrhage in Rat by Blocking Haem-Driven Inflammatory Pathology","volume":"5","author":"Greenhalgh","year":"2012","journal-title":"Dis Model Mech"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.788146\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T20:01:09Z","timestamp":1674590469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.788146\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":101,"alternative-id":["10.3389\/fimmu.2021.788146"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.788146","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]},"article-number":"788146"}}