{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:46:44Z","timestamp":1793738804834,"version":"4.6.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008871","name":"Yunnan Provincial Science and Technology Department","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007062","name":"Yangzhou University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The upper airway epithelium is the primary site of exposure to <jats:italic>Bordetella pertussis<\/jats:italic> and the initiator of host responses to this microbe. <jats:italic>B. pertussis<\/jats:italic> may cause serious respiratory infections resulting in major complications, as well as severe impairment of airway function. While pertussis treatment options are limited because the molecular responses in the upper respiratory tract in the early stages of infection have not been characterized. Here, we performed a genome-wide transcriptional analysis of nasal turbinates isolated from mice over 11 days after <jats:italic>B. pertussis<\/jats:italic> infection. Using RNA-seq, we characterized the differentially expressed genes and pathways associated with the changes in the nasal turbinates following infection. Statistical analysis revealed that infection is a dynamic process characterized by increased expression of a set of acute inflammatory responses at an early stage. After this initial inflammatory response, we observed increases in the levels of transcripts associated with the regulation of immune processes. In particular, we found that <jats:italic>B. pertussis<\/jats:italic> infection significantly increased the levels of type I interferons (IFNs) and related genes in the nasal turbinates at 2 h, 2 days, and 4 days postinfection. Therefore, we investigated the role of type I IFNs in <jats:italic>B. pertussis<\/jats:italic> infection in type I IFNs receptor-deficient (IFNAR1<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. There was no difference in bacterial clearance or adaptive immune responses between wild-type and IFNAR1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. However, a lack of type I IFNs signaling ameliorated pulmonary immunopathology, reduced the production of inflammatory cytokines and limited the recruitment of neutrophils to the lung during <jats:italic>B. pertussis<\/jats:italic> infection. Thus, our findings suggest that inhibiting the effects of type I IFNs may contribute to dampening inflammation, which could be an approach for the treatment of <jats:italic>B. pertussis<\/jats:italic> infection and management of the associated disease symptoms.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1521970","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T05:23:36Z","timestamp":1741325016000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Bordetella pertussis infection activates the type I interferon signaling pathway to exacerbate respiratory tract inflammatory response"],"prefix":"10.3389","volume":"16","author":[{"given":"Wenwen","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangli","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukui","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingbo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-an","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1001\/jama.2024.9049","article-title":"What is pertussis","volume":"332","author":"Scruggs-Wodkowski","year":"2024","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2389086","DOI":"10.1080\/22221751.2024.2389086","article-title":"Rising pertussis cases and deaths in China: current trends and clinical solutions","volume":"13","author":"Yahong","year":"2024","journal-title":"Emerg Microbes Infect"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01064-8","article-title":"Pertussis vaccines, epidemiology and evolution","volume":"22","author":"Domenech de Cell\u00e8s","year":"2024","journal-title":"Nat Rev Microbiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2400459","DOI":"10.2807\/1560-7917.ES.2024.29.31.2400459","article-title":"Resurgence of Bordetella pertussis, including one macrolide-resistant isolate, France, 2024","volume":"29","author":"Rodrigues","year":"2024","journal-title":"Euro Surveill"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2400301","DOI":"10.2807\/1560-7917.ES.2024.29.23.2400301","article-title":"Pertussis outbreak in neonates and young infants across Italy, January to May 2024: implications for vaccination strategies","volume":"29","author":"Poeta","year":"2024","journal-title":"Euro Surveill"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200850","article-title":"Waning protection after fifth dose of acellular pertussis vaccine in children","volume":"367","author":"Klein","year":"2012","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.16.24305932","article-title":"Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused by ptxP3 macrolide-resistant Bordetella pertussis MT28 clone in China","volume":"30","author":"Fu","year":"2024","journal-title":"Clin Microbiol Infect"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03068","article-title":"The role of mucosal immunity in pertussis","volume":"9","author":"Solans","year":"2018","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00110-13","article-title":"Quantification of the adenylate cyclase toxin of Bordetella pertussis in vitro and during respiratory infection","volume":"81","author":"Eby","year":"2013","journal-title":"Infect Immun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2021.1980987","article-title":"Pathogenicity and virulence of Bordetella pertussis and its adaptation to its strictly human host","volume":"12","author":"Belcher","year":"2021","journal-title":"Virulence"},{"key":"B11","doi-asserted-by":"publisher","first-page":"dmm049266","DOI":"10.1242\/dmm.049266","article-title":"Modeling the catarrhal stage of Bordetella pertussis upper respiratory tract infections in mice","volume":"15","author":"Soumana","year":"2022","journal-title":"Dis Model Mech"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nri1777","article-title":"Mucosal vaccines: the promise and the challenge","volume":"6","author":"Neutra","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4713","DOI":"10.1016\/j.cell.2021.07.023","article-title":"Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19","volume":"184","author":"Ziegler","year":"2021","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.99025","article-title":"Nasal priming by a murine coronavirus provides protective immunity against lethal heterologous virus pneumonia","volume":"3","author":"Hua","year":"2018","journal-title":"JCI Insight"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01478.x","article-title":"Induction of type I interferons by bacteria","volume":"12","author":"Monroe","year":"2010","journal-title":"Cell Microbiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.01.007","article-title":"Impact of type I interferons on susceptibility to bacterial pathogens","volume":"29","author":"Peignier","year":"2021","journal-title":"Trends Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.878832","article-title":"Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model","volume":"13","author":"Jiang","year":"2022","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.757375","article-title":"Dose-sparing intradermal DTaP-sIPV immunization with a hollow microneedle leads to superior immune responses","volume":"12","author":"Zuo","year":"2021","journal-title":"Front Microbiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"110112","DOI":"10.1016\/j.celrep.2021.110112","article-title":"A two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge","volume":"37","author":"Jiang","year":"2021","journal-title":"Cell Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp1137","article-title":"The Sanger FASTQ file format for sequences with quality scores, and the Solexa\/Illumina FASTQ variants","volume":"38","author":"Cock","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat Methods"},{"key":"B24","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinf"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-98141-3","volume-title":"ggplot2: elegant graphics for data analysis","author":"Wickham","year":"2009"},{"key":"B28","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/1471-2105-7-191","article-title":"STEM: a tool for the analysis of short time series gene expression data","volume":"7","author":"Ernst","year":"2006","journal-title":"BMC Bioinf"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.12.025","article-title":"Dynamic profiles of neutralizing antibody responses elicited in rhesus monkeys immunized with a combined tetravalent DTaP-Sabin IPV candidate vaccine","volume":"32","author":"Sun","year":"2014","journal-title":"Vaccine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e104548","DOI":"10.1371\/journal.pone.0104548","article-title":"Molecular signatures of the evolving immune response in mice following a Bordetella pertussis infection","volume":"9","author":"Raeven","year":"2014","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900912","article-title":"Age-dependent effects of type I and type III IFNs in the pathogenesis of bordetella pertussis infection and disease","volume":"204","author":"Ardanuy","year":"2020","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.idm.2019.06.001","article-title":"Investigation of temporal and spatial heterogeneities of the immune responses to Bordetella pertussis infection in the lung and spleen of mice via analysis and modeling of dynamic microarray gene expression data","volume":"4","author":"Deng","year":"2019","journal-title":"Infect Dis Model"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e2100153","DOI":"10.1002\/mnfr.202100153","article-title":"Copper-binding peptides attenuate microglia inflammation through suppression of NF-kB pathway","volume":"65","author":"Caetano-Silva","year":"2021","journal-title":"Mol Nutr Food Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/s41392-023-01620-3","article-title":"The IL-17 family in diseases: from bench to bedside","volume":"8","author":"Huangfu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00895-08","article-title":"Pertussis toxin inhibits early chemokine production to delay neutrophil recruitment in response to Bordetella pertussis respiratory tract infection in mice","volume":"76","author":"Andreasen","year":"2008","journal-title":"Infect Immun"},{"key":"B36","doi-asserted-by":"publisher","first-page":"ftv081","DOI":"10.1093\/femspd\/ftv081","article-title":"Review of the neutrophil response to Bordetella pertussis infection","volume":"73","author":"Eby","year":"2015","journal-title":"Pathog Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e1010402","DOI":"10.1371\/journal.ppat.1010402","article-title":"The Fim and FhaB adhesins play a crucial role in nasal cavity infection and Bordetella pertussis transmission in a novel mouse catarrhal infection model","volume":"18","author":"Holubova","year":"2022","journal-title":"PloS Pathog"},{"key":"B38","doi-asserted-by":"publisher","first-page":"ftw087","DOI":"10.1093\/femspd\/ftw087","article-title":"Pertussis leukocytosis: mechanisms, clinical relevance and treatment","volume":"74","author":"Carbonetti","year":"2016","journal-title":"Pathog Dis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.014","article-title":"Sensing of bacterial cyclic dinucleotides by the oxidoreductase RECON promotes NF-\u03baB activation and shapes a proinflammatory antibacterial state","volume":"46","author":"McFarland","year":"2017","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.274","article-title":"RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids","volume":"31","author":"Abdullah","year":"2012","journal-title":"EMBO J"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.11.002","article-title":"TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA","volume":"4","author":"Charrel-Dennis","year":"2008","journal-title":"Cell Host Microbe"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201055","article-title":"Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9","volume":"189","author":"Parker","year":"2012","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"103161","DOI":"10.1016\/j.autrev.2022.103161","article-title":"Friend or foe: RIG- I like receptors and diseases","volume":"21","author":"Song","year":"2022","journal-title":"Autoimmun Rev"},{"key":"B44","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.chom.2019.10.004","article-title":"An RNA-binding protein secreted by a bacterial pathogen modulates RIG-I signaling","volume":"26","author":"Pagliuso","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01006-14","article-title":"RIG-I detects mRNA of intracellular Salmonella enterica serovar Typhimurium during bacterial infection","volume":"5","author":"Schmolke","year":"2014","journal-title":"mBio"},{"key":"B46","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s12964-023-01263-5","article-title":"Functional diversity of c-di-GMP receptors in prokaryotic and eukaryotic systems","volume":"21","author":"Khan","year":"2023","journal-title":"Cell Commun Signal"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nature10429","article-title":"STING is a direct innate immune sensor of cyclic di-GMP","volume":"478","author":"Burdette","year":"2011","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00475-17","article-title":"Activation of bvg-repressed genes in bordetella pertussis by risA requires cross talk from noncooperonic histidine kinase risK","volume":"199","author":"Chen","year":"2017","journal-title":"J Bacteriol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2460","article-title":"The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response","volume":"13","author":"Parvatiyar","year":"2012","journal-title":"Nat Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2023.0066","article-title":"DNA-dependent interferon induction and lung inflammation in bordetella pertussis infection","volume":"43","author":"Ardanuy","year":"2023","journal-title":"J Interferon Cytokine Res"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0421-x","article-title":"Decoding type I and III interferon signalling during viral infection","volume":"4","author":"Mesev","year":"2019","journal-title":"Nat Microbiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.101","article-title":"Plasmacytoid dendritic cell-derived IFN\u03b1 modulates Th17 differentiation during early Bordetella pertussis infection in mice","volume":"9","author":"Wu","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"5566","DOI":"10.1038\/s41467-020-19412-6","article-title":"Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis","volume":"11","author":"Moreira-Teixeira","year":"2020","journal-title":"Nat Commun"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e1012368","DOI":"10.1371\/journal.ppat.1012368","article-title":"The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons","volume":"20","author":"Cabrera","year":"2024","journal-title":"PloS Pathog"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00333-14","article-title":"Alpha\/beta interferon receptor signaling amplifies early proinflammatory cytokine production in the lung during respiratory syncytial virus infection","volume":"88","author":"Goritzka","year":"2014","journal-title":"J Virol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1521970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T05:23:42Z","timestamp":1741325022000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1521970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,7]]},"references-count":55,"alternative-id":["10.3389\/fimmu.2025.1521970"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1521970","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,7]]},"article-number":"1521970"}}