{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:35:10Z","timestamp":1760236510972,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["RP11916B6AEB0D37"],"award-info":[{"award-number":["RP11916B6AEB0D37"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Following a Chlamydia\u00a0trachomatis infection, the host immune response is characterized by its recognition via Toll-like and Nod-like Receptors, and the subsequent activation of interferon (IFN)-\u03b3-mediated signaling pathways. Recently, the inflammasome-mediated host cell response has emerged to play a role in the physiopathology of C. trachomatis infection. Here we investigated, for the first time, the interaction of IFN-\u03b3 and inflammasome in an in vitro model of C. trachomatis-infected primary human synovial cells. Chlamydial replication as well as the expression of caspase-1, IL-1\u03b2, as well as IL-18 and IL-6, were assayed. Our results demonstrated the inhibitory activity of IFN-\u03b3 by interfering with the inflammasome network through the downregulation of caspase-1 mRNA expression. In addition, the ability of C. trachomatis to hinder the inflammasome pathway favoring its intracellular survival within synovial cells, was observed. Overall, our data suggest a potential mechanism of immune evasion by C. trachomatis in synovial cells, that may be contested by IFN-\u03b3.<\/jats:p>","DOI":"10.3390\/life11121359","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T20:23:21Z","timestamp":1638908601000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potential IFN\u03b3 Modulation of Inflammasome Pathway in Chlamydia trachomatis Infected Synovial Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-8588","authenticated-orcid":false,"given":"Simone","family":"Filardo","sequence":"first","affiliation":[{"name":"Section of Microbiology, Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0197-0485","authenticated-orcid":false,"given":"Marisa","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Frasca","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Diaco","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirko","family":"Scordio","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1044-1478","authenticated-orcid":false,"given":"Carolina","family":"Scagnolari","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Sessa","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: Global prevalence and incidence estimates, 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull. World Health Organ."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Di Pietro, M., Filardo, S., Romano, S., and Sessa, R. (2019). Chlamydia trachomatis and Chlamydia pneumoniae Interaction with the Host: Latest Advances and Future Prospective. Microorganisms, 7.","DOI":"10.3390\/microorganisms7050140"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"390","DOI":"10.15698\/mic2016.09.525","article-title":"Chlamydia trachomatis Genital Infections","volume":"3","author":"Ferone","year":"2016","journal-title":"Microb. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"508071","DOI":"10.1155\/2015\/508071","article-title":"Effects ofMentha suaveolensEssential Oil onChlamydia trachomatis","volume":"2015","author":"Sessa","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_5","first-page":"977","article-title":"Chlamydia trachomatis elicits TLR3 expression but disrupts the inflammatory signaling down-modulating NF\u03baB and IRF3 transcription factors in human Sertoli cells","volume":"34","author":"Filardo","year":"2020","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5847","DOI":"10.1038\/s41598-019-42396-3","article-title":"Growth kinetics of Chlamydia trachomatis in primary human Sertoli cells","volume":"9","author":"Filardo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18689\/ijmr-1000101","article-title":"TLR3 Deficiency Leads to a Dysregulation in the Global Gene-Expression Profile in Murine Oviduct Epithelial Cells Infected with Chlamydia muridarum","volume":"1","author":"Kumar","year":"2018","journal-title":"Int. J. Microbiol. Curr. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"ftw076","DOI":"10.1093\/femspd\/ftw076","article-title":"STAT3-mediated TLR2\/4 pathway upregulation in an IFN-gamma-inducedChlamydia trachomatispersistent infection model","volume":"74","author":"Yu","year":"2016","journal-title":"Pathog. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/mi.2012.63","article-title":"Nod1, but not the ASC inflammasome, contributes to induction of IL-1\u03b2 secretion in human trophoblasts after sensing of Chlamydia trachomatis","volume":"6","author":"Kavathas","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1128\/IAI.00104-08","article-title":"The Cytosolic Pattern Recognition Receptor NOD1 Induces Inflammatory Interleukin-8 during Chlamydia trachomatis Infection","volume":"76","author":"Buchholz","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Di Pietro, M., Filardo, S., Frasca, F., Scagnolari, C., Manera, M., Sessa, V., Antonelli, G., and Sessa, R. (2020). Interferon-\u03b3 Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia trachomatis Infection Model of Primary Human Synovial Fibroblasts. Microorganisms, 8.","DOI":"10.3390\/microorganisms8020235"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.3389\/fmicb.2019.02329","article-title":"Chlamydial Infection From Outside to Inside","volume":"10","author":"Gitsels","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.3389\/fmicb.2018.03101","article-title":"Chlamydia Persistence: A Survival Strategy to Evade Antimicrobial Effects in-vitro and in-vivo","volume":"9","author":"Panzetta","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.ijmm.2014.04.006","article-title":"Effects of vaginal lactobacilli in Chlamydia trachomatis infection","volume":"304","author":"Mastromarino","year":"2014","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.coi.2019.05.001","article-title":"Host inflammasome defense mechanisms and bacterial pathogen evasion strategies","volume":"60","author":"Brewer","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/imr.12534","article-title":"Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases","volume":"277","author":"Man","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.joca.2018.02.901","article-title":"NLRP3 as a potentially novel biomarker for the management of osteoarthritis","volume":"26","author":"McAllister","year":"2018","journal-title":"Osteoarthr. Cartil."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrrheum.2010.159","article-title":"The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis","volume":"6","author":"Sellam","year":"2010","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"561459","DOI":"10.1155\/2014\/561459","article-title":"The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis","volume":"2014","author":"Wojdasiewicz","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1172\/JCI1379","article-title":"Interleukin-18 (IFNgamma-inducing factor) induces IL-8 and IL-1beta via TNFalpha production from non-CD14+ human blood mononuclear cells","volume":"101","author":"Puren","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1749-6632.1998.tb08307.x","article-title":"Interleukin-1beta, Interleukin-18, and the Interleukin-1beta Converting Enzymea","volume":"856","author":"Dinarello","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.3389\/fimmu.2018.01981","article-title":"An Adaptive Chlamydia trachomatis-Specific IFN-\u03b3-Producing CD4+ T Cell Response Is Associated with Protection Against Chlamydia Reinfection in Women","volume":"9","author":"Bakshi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ziklo, N., Huston, W.M., Taing, K., Katouli, M., and Timms, P. (2016). In vitro rescue of genital strains of Chlamydia trachomatis from interferon-\u03b3 and tryptophan depletion with indole-positive, but not indole-negative Prevotella spp.. BMC Microbiol., 16.","DOI":"10.1186\/s12866-016-0903-4"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"ftx054","DOI":"10.1093\/femspd\/ftx054","article-title":"Lactobacilli\u2013lactoferrin interplay in Chlamydia trachomatis infection","volume":"75","author":"Sessa","year":"2017","journal-title":"Pathog. Dis."},{"key":"ref_25","first-page":"509","article-title":"Resveratrol in Chlamydia pneumoniae-induced foam cell formation and interleukin-17A synthesis","volume":"27","author":"Schiavoni","year":"2013","journal-title":"J. Boil. Regul. Homeost. Agents"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.chom.2011.06.008","article-title":"The Chlamydia Protease CPAF Regulates Host and Bacterial Proteins to Maintain Pathogen Vacuole Integrity and Promote Virulence","volume":"10","author":"Jorgensen","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"26789","DOI":"10.1074\/jbc.M109.026823","article-title":"Inflammasome-dependent Caspase-1 Activation in Cervical Epithelial Cells Stimulates Growth of the Intracellular Pathogen Chlamydia trachomatis","volume":"284","author":"Koo","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107667","DOI":"10.1016\/j.celrep.2020.107667","article-title":"hGBP1 Coordinates Chlamydia Restriction and Inflammasome Activation through Sequential GTP Hydrolysis","volume":"31","author":"Xavier","year":"2020","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Webster, S.J., Brode, S., Ellis, L., Fitzmaurice, T., Elder, M.J., Gekara, N.O., Tourlomousis, P., Bryant, C., Clare, S., and Chee, R. (2017). Detection of a microbial metabolite by STING regulates inflammasome activation in response to Chlamydia trachomatis infection. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006383"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4740","DOI":"10.1128\/IAI.00856-15","article-title":"Guanylate Binding Proteins Enable Rapid Activation of Canonical and Noncanonical Inflammasomes in Chlamydia-Infected Macrophages","volume":"83","author":"Finethy","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.micinf.2010.04.008","article-title":"Chlamydial infection of monocytes stimulates IL-1\u03b2 secretion through activation of the NLRP3 inflammasome","volume":"12","author":"Padilla","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bj.2016.10.003","article-title":"The inflammasome: Friend or foe in Chlamydia infection?","volume":"39","author":"Walton","year":"2016","journal-title":"Biomed. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1136\/gut.49.2.251","article-title":"Interferon gamma inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis","volume":"49","author":"Detjen","year":"2001","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1023\/B:NEON.0000021896.52664.9e","article-title":"Caspase-1 Mediates Fas-Induced Apoptosis and is Up-Regulated by Interferon- in Human Astrocytoma Cells","volume":"67","author":"Choi","year":"2004","journal-title":"J. Neuro-Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"39920","DOI":"10.1074\/jbc.M007255200","article-title":"Expression Analysis of the Human Caspase-1 Subfamily Reveals Specific Regulation of the CASP5 Gene by Lipopolysaccharide and Interferon-\u03b3","volume":"275","author":"Lin","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/ni.2829","article-title":"The PYRIN domain\u2013only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses","volume":"15","author":"Khare","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nri1551","article-title":"Immunology of Chlamydia infection: Implications for a Chlamydia trachomatis vaccine","volume":"5","author":"Brunham","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.3389\/fimmu.2021.639834","article-title":"Insights Into Host Cell Cytokines in Chlamydia Infection","volume":"12","author":"Xiang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1002\/(SICI)1521-4141(199911)29:11<3782::AID-IMMU3782>3.0.CO;2-B","article-title":"IFN-Gamma Knockout Mice Show Th2-Associated Delayed-Type Hypersensitivity and the Inflammatory Cells Fail to Localize and Control Chlamydial Infection","volume":"29","author":"Wang","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"153712","DOI":"10.1016\/j.phymed.2021.153712","article-title":"Cascade of immune mechanism and consequences of inflammatory disorders","volume":"91","author":"Megha","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Eitel, J., Meixenberger, K., Van Laak, C., Orlovski, C., Hocke, A., Schmeck, B., Hippenstiel, S., N\u2019Guessan, P.D., Suttorp, N., and Opitz, B. (2012). Rac1 Regulates the NLRP3 Inflammasome Which Mediates IL-1beta Production in Chlamydophila pneumoniae Infected Human Mononuclear Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030379"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"417658","DOI":"10.1155\/2009\/417658","article-title":"Persistently Elevated Level of IL-8 inChlamydia trachomatisInfected HeLa 229 Cells is Dependent on Intracellular Available Iron","volume":"2009","author":"Vardhan","year":"2009","journal-title":"Mediat. Inflamm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/embor.2010.93","article-title":"Regulation of interleukin-1\u03b2 by interferon-\u03b3 is species specific, limited by suppressor of cytokine signalling 1 and influences interleukin-17 production","volume":"11","author":"Masters","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1182\/blood.V83.2.537.537","article-title":"Interferon-Gamma Upregulates In-terleukin-8 Gene Expression in Human Monocytic Cells by a Posttranscriptional Mechanism","volume":"83","author":"Bosco","year":"1994","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0065-2776(08)60642-2","article-title":"Interleukin-1 and Its Biologically Related Cytokines","volume":"44","author":"Dinarello","year":"1989","journal-title":"Adv. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.4049\/jimmunol.140.7.2267","article-title":"Human pro-IL-1 beta gene expression in monocytic cells is regulated by two distinct pathways","volume":"140","author":"Fenton","year":"1988","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.4049\/jimmunol.138.11.3972","article-title":"Transcriptional regulation of the human prointerleukin 1 beta gene","volume":"138","author":"Fenton","year":"1987","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.4049\/jimmunol.137.10.3189","article-title":"Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate","volume":"137","author":"Knudsen","year":"1986","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jss.2006.09.037","article-title":"Interleukin-6 Protein Expression Is More Important Than Interleukin-6 mRNA Levels in Assessing Surgical Invasiveness","volume":"142","author":"Huang","year":"2007","journal-title":"J. Surg. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/imr.12051","article-title":"Post-transcriptional regulatory networks in immunity","volume":"253","author":"Ivanov","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"847","DOI":"10.3389\/fimmu.2018.00847","article-title":"Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion","volume":"9","author":"Castro","year":"2018","journal-title":"Front. Immunol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/12\/1359\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:42:49Z","timestamp":1760168569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/12\/1359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,7]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["life11121359"],"URL":"https:\/\/doi.org\/10.3390\/life11121359","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2021,12,7]]}}}