{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:46:52Z","timestamp":1787240812776,"version":"build-2736575974"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Lyme borreliosis is an emerging tick-borne disease caused by spirochetes\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    sensu lato. In Europe, Lyme borreliosis is predominantly caused by\n                    <jats:italic>Borrelia afzelii<\/jats:italic>\n                    and transmitted by\n                    <jats:italic>Ixodes ricinus<\/jats:italic>\n                    . Although\n                    <jats:italic>Borrelia<\/jats:italic>\n                    behavior throughout tick development is quite well documented, specific molecular interactions between\n                    <jats:italic>Borrelia<\/jats:italic>\n                    and the tick have not been satisfactorily examined. Here, we present the first transcriptomic study focused on the expression of tick midgut genes regulated by\u00a0\n                    <jats:italic>Borrelia<\/jats:italic>\n                    . By using massive analysis of cDNA ends (MACE), we searched for tick transcripts expressed differentially in the midgut of unfed, 24h-fed, and fully fed\n                    <jats:italic>I. ricinus<\/jats:italic>\n                    nymphs infected with\n                    <jats:italic>B. afzelii<\/jats:italic>\n                    . In total, we identified 553 upregulated and 530 downregulated tick genes and demonstrated that\n                    <jats:italic>B. afzelii<\/jats:italic>\n                    interacts intensively with the tick. Technical and biological validations confirmed the accuracy of the transcriptome. The expression of five validated tick genes was silenced by RNA interference. Silencing of the uncharacterized protein (GXP_Contig_30818) delayed the infection progress and decreased infection prevalence in the target mice tissues. Silencing of other genes did not significantly affect tick feeding nor the transmission of\n                    <jats:italic>B. afzelii<\/jats:italic>\n                    , suggesting a possible role of these genes rather in\n                    <jats:italic>Borrelia<\/jats:italic>\n                    acquisition or persistence in ticks. Identification of genes and proteins exploited by\n                    <jats:italic>Borrelia<\/jats:italic>\n                    during transmission and establishment in a tick could help the development of novel preventive strategies for Lyme borreliosis.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2020.612412","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T01:15:39Z","timestamp":1612401339000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of Tick Ixodes ricinus Midgut Genes Differentially Expressed During the Transmission of Borrelia afzelii Spirochetes Using a Transcriptomic Approach"],"prefix":"10.3389","volume":"11","author":[{"given":"Sazzad","family":"Mahmood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radek","family":"Sima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Urbanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos J. A.","family":"Trentelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Krezdorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Winter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Kopacek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joppe W.","family":"Hovius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Hajdusek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","author":"Steere","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m1041","article-title":"Lyme borreliosis: Diagnosis and management","author":"Kullberg","year":"2020","journal-title":"BMJ"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2807\/ese.16.27.19906-en","article-title":"Lyme borreliosis in Europe","volume":"16","author":"Rizzoli","year":"2011","journal-title":"Euro Surveill"},{"key":"B4","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.idc.2015.02.010","article-title":"Epidemiology of Lyme Disease","volume":"29","author":"Mead","year":"2015","journal-title":"Infect Dis Clin North Am"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60103-7","article-title":"Lyme borreliosis","volume":"379","author":"Stanek","year":"2012","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199807233390401","article-title":"Vaccination against lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant","volume":"339","author":"Steere","year":"1998","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00917-19","article-title":"Broadly protective multivalent OspA vaccine against lyme borreliosis, developed based on surface shaping of the C-terminal fragment","author":"Nayak","year":"2020","journal-title":"Infect Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-020-0183-8","article-title":"Design of a broadly reactive Lyme disease vaccine","author":"Kamp","year":"2020","journal-title":"NPJ Vaccines"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184357","article-title":"The novel Lyme borreliosis vaccine VLA15 shows broad protection against Borrelia species expressing six different OspA serotypes","volume":"12","author":"Comstedt","year":"2017","journal-title":"PLoS One"},{"key":"B10","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s13071-019-3468-x","article-title":"Counterattacking the tick bite: towards a rational design of anti-tick vaccines targeting pathogen transmission","volume":"12","author":"Rego","year":"2019","journal-title":"Parasit Vectors"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00609-17","article-title":"Europe-wide meta-analysis of Borrelia burgdorferi sensu lato prevalence in questing Ixodes ricinus ticks","volume":"83","author":"Strnad","year":"2017","journal-title":"Appl Environ Microbiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00896-18","article-title":"Tracking of Borrelia afzelii transmission from infected Ixodes ricinus nymphs to mice","volume":"87","author":"Pospisilova","year":"2019","journal-title":"Infect Immun"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00026","article-title":"Interaction of the tick immune system with transmitted pathogens","volume":"3","author":"Hajdu\u0161ek","year":"2013","journal-title":"Front Cell Infect Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39401","article-title":"Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks","volume":"119","author":"Dunham-Ems","year":"2009","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2013.04.002","article-title":"New insights into the machinery of blood digestion by ticks","volume":"29","author":"Sojka","year":"2013","journal-title":"Trends Parasitol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00211","article-title":"Poor Unstable Midgut Microbiome of Hard Ticks Contrasts With Abundant and Stable Monospecific Microbiome in Ovaries","author":"Guizzo","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12882","article-title":"Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation","author":"Iyer","year":"2015","journal-title":"Mol Microbiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.1.271","article-title":"Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine","author":"De Silva","year":"1996","journal-title":"J Exp Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.10.027","article-title":"TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi","volume":"119","author":"Pal","year":"2004","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nature03812","article-title":"The Lyme disease agent exploits a tick protein to infect the mammalian host","volume":"436","author":"Ramamoorthi","year":"2005","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2012.12.010","article-title":"Ixodes ricinus ticks infected with the causative agent of Lyme disease, Borrelia burgdorferi sensu lato, have higher energy reserves","volume":"43","author":"Herrmann","year":"2013","journal-title":"Int J Parasitol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1603\/me10111","article-title":"Survival of Ixodes ricinus (Acari: Ixodidae) Under Challenging Conditions of Temperature and Humidity Is Influenced by Borrelia burgdorferi sensu lato Infection","volume":"47","author":"Herrmann","year":"2010","journal-title":"J Med Entomol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S0934-8840(00)80005-5","article-title":"Identification of Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii in Ixodes ricinus Ticks from Southern Bohemia Using Monoclonal Antibodies","volume":"289","author":"\u0160t\u011bp\u00e1nov\u00e1-Tresov\u00e1","year":"2000","journal-title":"Zentralblatt f\u00fcr Bakteriol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3103","article-title":"IL-37 requires the receptors IL-18R\u03b1 and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction","volume":"16","author":"Nold-Petry","year":"2015","journal-title":"Nat Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","author":"Martin","year":"2011","journal-title":"EMBnet.journal"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp612","article-title":"DEGseq: An R package for identifying differentially expressed genes from RNA-seq data","volume":"26","author":"Wang","year":"2010","journal-title":"Bioinformatics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.dci.2014.09.004","article-title":"Thioester-containing proteins of the tick Ixodes ricinus: Gene expression, response to microbial challenge and their role in phagocytosis of the yeast Candida albicans","volume":"48","author":"Urbanov\u00e1","year":"2015","journal-title":"Dev Comp Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00267-7","article-title":"Conserved Role of a Complement-like Protein in Phagocytosis Revealed by dsRNA Knockout in Cultured Cells of the Mosquito, Anopheles gambiae","volume":"104","author":"Levashina","year":"2001","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807961106","article-title":"Knockdown of proteins involved in iron metabolism limits tick reproduction and development","volume":"106","author":"Hajdusek","year":"2009","journal-title":"Proc Natl Acad Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00509","article-title":"Characterization of Ixodes ricinus Fibrinogen-Related Proteins (Ixoderins) Discloses Their Function in the Tick Innate Immunity","volume":"7","author":"Honig Mondekova","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4161\/epi.26931","article-title":"Massive analysis of cDNA Ends (MACE) and miRNA expression profiling identifies proatherogenic pathways in chronic kidney disease","volume":"9","author":"Zawada","year":"2014","journal-title":"Epigenetics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"20061","DOI":"10.1038\/s41598-020-76268-y","article-title":"A combined transcriptomic approach to identify candidates for an anti-tick vaccine blocking B. afzelii transmission","volume":"10","author":"Trentelman","year":"2020","journal-title":"Sci Rep"},{"key":"B34","doi-asserted-by":"publisher","first-page":"297","DOI":"10.12688\/f1000research.13635.1","article-title":"A draft genome sequence for the Ixodes scapularis cell line, ISE6","volume":"7","author":"Miller","year":"2018","journal-title":"F1000Research"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2007.05.008","article-title":"Behind the scene, something else is pulling the strings: Emphasizing parasitic manipulation in vector-borne diseases","author":"Lef\u00e8vre","year":"2008","journal-title":"Infect Genet Evol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2005.11.005","article-title":"An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks","author":"Ribeiro","year":"2006","journal-title":"Insect Biochem Mol Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1603\/0022-2585(2005)042[0036:deoirt]2.0.co;2","article-title":"Differential Expression of Ixodes ricinus Tick Genes Induced by Blood Feeding or Borrelia burgdorferi Infection","author":"Rudenko","year":"2006","journal-title":"J Med Entomol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1603\/0022-2585-37.2.265","article-title":"Response of the Tick Dermacentor variabilis (Acari: Ixodidae) to Hemocoelic Inoculation of Borrelia burgdorferi (Spirochetales)","volume":"37","author":"Johns","year":"2009","journal-title":"J Med Entomol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025354326877","article-title":"Expression of defensin-like peptides in tick hemolymph and midgut in response to challenge with Borrelia burgdorferi, Escherichia coli and Bacillus subtilis","volume":"28","author":"Sonenshine","year":"2002","journal-title":"Exp Appl Acarology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001205","article-title":"Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the Lyme disease agent","volume":"6","author":"Dai","year":"2010","journal-title":"PLoS Pathog"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-015-1365-0","article-title":"Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut","author":"Coumou","year":"2016","journal-title":"J Mol Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00208-0","article-title":"Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization","author":"Narasimhan","year":"2017","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2019.06.002","article-title":"Borrelia burgdorferi chemotaxis toward tick protein Salp12 contributes to acquisition","author":"Murfin","year":"2019","journal-title":"Ticks Tick Borne Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1990.42.352","article-title":"Growth kinetics of the lyme disease spirochete (Borrelia burgdorferi) in vector ticks (Ixodes dammini)","author":"Piesman","year":"1990","journal-title":"Am J Trop Med Hyg"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1134\/S1022795418040142","article-title":"The First Data on the TROSPA Gene Structure in Ixodes persulcatus and Ixodes ricinus Ticks from Russia","author":"Sorokina","year":"2018","journal-title":"Russ J Genet"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/BF00931028","article-title":"The peritrophic membrane of Ixodes ricinus","author":"Zhu","year":"1991","journal-title":"Parasitol Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.4.2739-2742.2001","article-title":"Borrelia burgdorferi proteins whose expression is similarly affected by culture temperature and pH","author":"Ramamoorthy","year":"2001","journal-title":"Infect Immun"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005791","article-title":"Two Different Virulence-Related Regulatory Pathways in Borrelia burgdorferi Are Directly Affected by Osmotic Fluxes in the Blood Meal of Feeding Ixodes Ticks","author":"Bontemps-Gallo","year":"2016","journal-title":"PLoS Pathog"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1995.53.397","article-title":"Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding","author":"De Silva","year":"1995","journal-title":"Am J Trop Med Hyg"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-017-2187-4","article-title":"The abundance of the Lyme disease pathogen Borrelia afzelii declines over time in the tick vector Ixodes ricinus","author":"Jacquet","year":"2017","journal-title":"Parasites Vectors"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199641","article-title":"Genomic and phenotypic characterization of Borrelia afzelii BO23 and Borrelia garinii CIP 103362","author":"Bontemps-Gallo","year":"2018","journal-title":"PLoS One"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.538272","article-title":"A dityrosine network mediated by dual oxidase and peroxidase influences the persistence of lyme disease pathogens within the vector","author":"Yang","year":"2014","journal-title":"J Biol Chem"},{"key":"B53","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.chom.2013.12.001","article-title":"Gut microbiota of the tick vector Ixodes scapularis modulate colonization of the Lyme disease spirochete","volume":"15","author":"Narasimhan","year":"2014","journal-title":"Cell Host Microbe"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.612412\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T01:15:45Z","timestamp":1612401345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.612412\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2020.612412"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.612412","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,4]]},"article-number":"612412"}}