{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T20:11:30Z","timestamp":1783195890223,"version":"3.54.6"},"reference-count":47,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31870889"],"award-info":[{"award-number":["31870889"]}]},{"name":"National Natural Science Foundation of China","award":["31070797"],"award-info":[{"award-number":["31070797"]}]},{"name":"National Natural Science Foundation of China","award":["19JCZDJC35800"],"award-info":[{"award-number":["19JCZDJC35800"]}]},{"name":"National Natural Science Foundation of China","award":["15JCZDJC34900"],"award-info":[{"award-number":["15JCZDJC34900"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["31870889"],"award-info":[{"award-number":["31870889"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["31070797"],"award-info":[{"award-number":["31070797"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["19JCZDJC35800"],"award-info":[{"award-number":["19JCZDJC35800"]}]},{"name":"Key Program of Tianjin Science and Technology Commission","award":["15JCZDJC34900"],"award-info":[{"award-number":["15JCZDJC34900"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The incidence of Chlamydia trachomatis respiratory infection is increasing, and its pathogenesis is still unclear. Pyroptosis, as a mode of inflammatory cell death, plays a vital role in the occurrence and development of Chlamydia trachomatis respiratory infection. In this study, the potential pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection were identified by constructing a mouse model of C. muridarum infection combined with bioinformatics analysis. Through in-depth analysis of the RNA sequencing data, 13 differentially expressed pyroptosis-related genes were screened, including 1 downregulated gene and 12 upregulated genes. Gene ontology (GO) analysis showed that these genes mainly regulate inflammatory responses and produce IL-1\u03b2. Protein\u2013protein interaction network analysis identified eight hub genes of interest: Tnf, Tlr2, Il1b, Nlrp3, Tlr9, Mefv, Zbp1 and Tnfaip3. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of C. muridarum-infected mice was significantly reduced, consistent with the bioinformatics results. At the same time, we detected elevated levels of caspase-3, gasdermin D and gasdermin E proteins in the lungs of C. muridarum-infected mice, demonstrating that Chlamydia trachomatis infection does induce pyroptosis. We then predicted nine miRNAs targeting these hub genes and constructed a key competitive endogenous RNA (ceRNA) network. In summary, we identified six key pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in Chlamydia trachomatis respiratory infections.<\/jats:p>","DOI":"10.3390\/ijms241713570","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T08:19:39Z","timestamp":1693556379000},"page":"13570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In Silico Identification and Validation of Pyroptosis-Related Genes in Chlamydia Respiratory Infection"],"prefix":"10.3390","volume":"24","author":[{"given":"Ruoyuan","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaini","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Tuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Tan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrmicro.2016.30","article-title":"Chlamydia cell biology and pathogenesis","volume":"14","author":"Elwell","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/1040841X.2020.1730300","article-title":"Chlamydia: What is on the outside does matter","volume":"46","author":"Gitsels","year":"2020","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_3","first-page":"35","article-title":"One Face of Chlamydia trachomatis: The Infectious Elementary Body","volume":"412","author":"Hayward","year":"2018","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.micinf.2017.11.008","article-title":"Insight in the biology of Chlamydia-related bacteria","volume":"20","author":"Bayramova","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861899","DOI":"10.3389\/fcimb.2022.861899","article-title":"The Impact of Lateral Gene Transfer in Chlamydia","volume":"12","author":"Marti","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1101\/gr.275509.121","article-title":"Characterization of transcript enrichment and detection bias in single-nucleus RNA-seq for mapping of distinct human adipocyte lineages","volume":"32","author":"Gupta","year":"2022","journal-title":"Genome Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41392-021-00507-5","article-title":"Pyroptosis: Mechanisms and diseases","volume":"6","author":"Yu","year":"2021","journal-title":"Signal. Transduct. Target Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13045-020-00946-7","article-title":"Ferroptosis, necroptosis, and pyroptosis in anticancer immunity","volume":"13","author":"Tang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.tcb.2017.05.005","article-title":"Gasdermins: Effectors of Pyroptosis","volume":"27","author":"Kovacs","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41586-021-04384-4","article-title":"Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis","volume":"602","author":"Deng","year":"2022","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/s41423-022-00905-x","article-title":"Role of pyroptosis in inflammation and cancer","volume":"19","author":"Wei","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100924","DOI":"10.1016\/j.mam.2020.100924","article-title":"An overview of the non-canonical inflammasome","volume":"76","author":"Downs","year":"2020","journal-title":"Mol. Aspects Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"Kayagaki","year":"2015","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e12563","DOI":"10.1111\/cpr.12563","article-title":"Role of pyroptosis in cardiovascular disease","volume":"52","author":"Zeng","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12974-014-0233-0","article-title":"NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model","volume":"12","author":"Tan","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41419-022-04664-5","article-title":"STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS)","volume":"13","author":"Culerier","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev-physiol-020518-114320","article-title":"Cell Death in the Lung: The Apoptosis-Necroptosis Axis","volume":"81","author":"Sauler","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.jinf.2020.01.015","article-title":"Ocular Chlamydia trachomatis infection, anti-Pgp3 antibodies and conjunctival scarring in Vanuatu and Tarawa, Kiribati before antibiotic treatment for trachoma","volume":"80","author":"Butcher","year":"2020","journal-title":"J. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1093\/cid\/ciz429","article-title":"Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients","volume":"69","author":"Hoebe","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41572-022-00359-5","article-title":"Trachoma","volume":"8","author":"Solomon","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.4049\/jimmunol.2000957","article-title":"IL-27\/IL-27R Mediates Protective Immunity against Chlamydial Infection by Suppressing Excessive Th17 Responses and Reducing Neutrophil Inflammation","volume":"206","author":"Zha","year":"2021","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3389\/fcimb.2019.00392","article-title":"Early Transcriptional Landscapes of Chlamydia trachomatis-Infected Epithelial Cells at Single Cell Resolution","volume":"9","author":"Hayward","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"717311","DOI":"10.3389\/fimmu.2021.717311","article-title":"Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes","volume":"12","author":"Virok","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e0086422","DOI":"10.1128\/mbio.00864-22","article-title":"A Reverse Genetic Approach for Studying sRNAs in Chlamydia trachomatis","volume":"13","author":"Wang","year":"2022","journal-title":"mBio"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1116335","DOI":"10.3389\/fcimb.2023.1116335","article-title":"GSDMD-mediated pyroptosis restrains intracellular Chlamydia trachomatis growth in macrophages","volume":"13","author":"Jiang","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chu, J., Li, X., Qu, G., Wang, Y., Li, Q., Guo, Y., Hou, L., Liu, J., Eko, F.O., and He, C. (2020). Correction: Chlamydia psittaci PmpD-N modulated Chicken Macrophage Function by Triggering Th2 Polarization and the TLR2\/MyD88\/NF-\u03baB Signaling Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062003"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5454","DOI":"10.1038\/s41467-021-25749-3","article-title":"Chlamydia evasion of neutrophil host defense results in NLRP3 dependent myeloid-mediated sterile inflammation through the purinergic P2X7 receptor","volume":"12","author":"Yang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.immuni.2020.02.012","article-title":"Mitochondrial GSDMD Pores DAMPen Pyroptosis","volume":"52","author":"Barnett","year":"2020","journal-title":"Immunity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.tibs.2016.10.004","article-title":"Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death","volume":"42","author":"Shi","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature22393","article-title":"Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin","volume":"547","author":"Wang","year":"2017","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.micinf.2017.11.011","article-title":"New concepts in Chlamydia induced inflammasome responses","volume":"20","author":"Webster","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.jhep.2017.11.040","article-title":"Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice","volume":"68","author":"Xu","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8813","DOI":"10.7150\/thno.62521","article-title":"Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment","volume":"11","author":"Hsu","year":"2021","journal-title":"Theranostics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/art.41963","article-title":"Attenuation of Rheumatoid Arthritis Through the Inhibition of Tumor Necrosis Factor-Induced Caspase 3\/Gasdermin E-Mediated Pyroptosis","volume":"74","author":"Zhai","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41586-020-2071-9","article-title":"Gasdermin E suppresses tumour growth by activating anti-tumour immunity","volume":"579","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109632","DOI":"10.1016\/j.intimp.2022.109632","article-title":"CircVAPA contributes to hyper-proliferation and inflammation of keratinocytes through miR-125b-5p\/sirt6 axis in psoriasis","volume":"115","author":"Chen","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102655","DOI":"10.1016\/j.redox.2023.102655","article-title":"miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1\/Nrf2\/GPX4 in sepsis lung injury","volume":"62","author":"Shen","year":"2023","journal-title":"Redox Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.phrs.2018.11.040","article-title":"Dioscin ameliorates intestinal ischemia\/reperfusion injury via adjusting miR-351-5p\/MAPK13-mediated inflammation and apoptosis","volume":"139","author":"Zheng","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jaci.2016.04.038","article-title":"MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2","volume":"139","author":"Kim","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, Mechanisms, and Significance of Macrophage Plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.tcb.2020.09.006","article-title":"Lipid Metabolism in Regulation of Macrophage Functions","volume":"30","author":"Yan","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1182\/blood.2019003990","article-title":"The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice","volume":"136","author":"Wu","year":"2020","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev-immunol-061020-053707","article-title":"Dendritic Cells Revisited","volume":"39","author":"Cardoso","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nri.2016.116","article-title":"Dendritic cell migration in health and disease","volume":"17","author":"Worbs","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s13054-021-03775-3","article-title":"Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury","volume":"25","author":"Jiao","year":"2021","journal-title":"Crit. Care"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/cmi.2016.68","article-title":"CD103+ lung dendritic cells (LDCs) induce stronger Th1\/Th17 immunity to a bacterial lung infection than CD11b(hi) LDCs","volume":"15","author":"Shekhar","year":"2018","journal-title":"Cell. Mol. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:44:50Z","timestamp":1760129090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,1]]},"references-count":47,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241713570"],"URL":"https:\/\/doi.org\/10.3390\/ijms241713570","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,1]]}}}