{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T18:31:18Z","timestamp":1763145078688,"version":"3.45.0"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00c3\u00b3n\/Agencia Estatal de Investigaci\u00c3\u00b3n","award":["MCIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033"]}]},{"name":"Spain and EU-FEDER","award":["BIOGAL PID2020-116761GB-I00"],"award-info":[{"award-number":["BIOGAL PID2020-116761GB-I00"]}]},{"DOI":"10.13039\/501100007480","name":"Universidad de Castilla-La Mancha","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007480","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Spain and the European Social Fund","award":["doctoral contract 2022-PRED-20675"],"award-info":[{"award-number":["doctoral contract 2022-PRED-20675"]}]},{"DOI":"10.13039\/501100021727","name":"Berlin University Alliance","doi-asserted-by":"publisher","award":["113_MC_GH_MEL-BER_Nijhof_FU"],"award-info":[{"award-number":["113_MC_GH_MEL-BER_Nijhof_FU"]}],"id":[{"id":"10.13039\/501100021727","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    <jats:italic>\n                      <jats:italic>Ixodes ricinus<\/jats:italic>\n                    <\/jats:italic>\n                    ticks (Acari: Ixodidae) are hematophagous ectoparasites and a major European vector of zoonotic diseases affecting global health. Tick salivary and midgut proteins antigen p23 (A0A0K8RKR7) and metalloprotease (A0A0K8RCY8) were previously implicated in the pathophysiology of the tick-borne allergy alpha-Gal syndrome (AGS). This study aimed to functionally characterize these two biomolecules, focusing on their role in\n                    <jats:italic>\n                      <jats:italic>I. ricinus<\/jats:italic>\n                    <\/jats:italic>\n                    tick feeding and reproduction through gene knockdown by RNA interference and midgut transcriptomic analysis. Validation of RNA-seq data was conducted using RT-qPCR analysis on tick midgut and salivary gland tissues. Silencing the expression of p23 and metalloprotease did not result in any significant differences in tick engorgement and egg batch weights compared to the control group. Gene set enrichment analysis following antigen p23 gene knockdown identified significantly upregulated pathways associated with protein production and suppressed routes mostly correlated with ion transport, lipid metabolism, catalytic activity, protein modification, and G-protein activity. Partial knockdown of the metalloprotease led to the upregulation of several biological and functional pathways associated with RNA splicing and significantly suppressed routes connected with detoxification, protein modification, catalytic activity and molecule binding. Antigen p23 appears to play a functional role in tick midgut cell homeostasis, primarily by participating in regulatory and signaling processes essential for cell viability. Metalloprotease is potentially involved in regulating midgut response to oxidative stress, thereby reducing tissue damage and promoting regular cell proliferation, growth and behavior. These results provide insights into tick physiology and bases for further research on tick-host interactions and AGS pathogenesis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0336570","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T18:26:07Z","timestamp":1763144767000},"page":"e0336570","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomics insights into the functional role of tick Ixodes ricinus proteins metalloprotease and antigen p23"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-7738","authenticated-orcid":true,"given":"Rita","family":"Vaz-Rodrigues","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent C.","family":"Duru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ard M.","family":"Nijhof","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7383-9649","authenticated-orcid":true,"given":"Jos\u00e9","family":"de la Fuente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"pone.0336570.ref001","doi-asserted-by":"crossref","first-page":"6938","DOI":"10.2741\/3200","article-title":"Overview: Ticks as vectors of pathogens that cause disease in humans and animals","volume":"13","author":"J de la Fuente","year":"2008","journal-title":"Front Biosci"},{"issue":"2","key":"pone.0336570.ref002","first-page":"60","article-title":"Ticks and Tick-Borne Infections: Complex Ecology, Agents, and Host Interactions","volume":"5","author":"SK Wikel","year":"2018","journal-title":"Vet Sci"},{"issue":"5","key":"pone.0336570.ref003","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3390\/pathogens12050633","article-title":"Advances in the Epidemiological Surveillance of Tick-Borne Pathogens","volume":"12","author":"AA D\u00edaz-S\u00e1nchez","year":"2023","journal-title":"Pathogens"},{"issue":"2","key":"pone.0336570.ref004","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.medmal.2019.01.007","article-title":"Ticks and tick-borne diseases","volume":"49","author":"N Boulanger","year":"2019","journal-title":"Med Mal Infect"},{"issue":"3","key":"pone.0336570.ref005","doi-asserted-by":"crossref","first-page":"101674","DOI":"10.1016\/j.ttbdis.2021.101674","article-title":"Tick exposures and alpha-gal syndrome: A systematic review of the evidence","volume":"12","author":"I Young","year":"2021","journal-title":"Ticks Tick Borne Dis"},{"key":"pone.0336570.ref006","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2147\/JAA.S265660","article-title":"Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)","volume":"15","author":"R Vaz-Rodrigues","year":"2022","journal-title":"J Asthma Allergy"},{"issue":"2","key":"pone.0336570.ref007","doi-asserted-by":"crossref","first-page":"102114","DOI":"10.1016\/j.ttbdis.2022.102114","article-title":"The biology of Ixodes ricinus with emphasis on its ecology","volume":"14","author":"O Kahl","year":"2023","journal-title":"Ticks and Tick-borne Diseases"},{"issue":"3","key":"pone.0336570.ref008","doi-asserted-by":"crossref","first-page":"301","DOI":"10.14202\/vetworld.2015.301-315","article-title":"Tick-borne infections in human and animal population worldwide","volume":"8","author":"J Brites-Neto","year":"2015","journal-title":"Vet World"},{"key":"pone.0336570.ref009","doi-asserted-by":"crossref","first-page":"680264","DOI":"10.3389\/fcimb.2021.680264","article-title":"Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack","volume":"11","author":"SR Sharma","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"issue":"2","key":"pone.0336570.ref010","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4049\/jimmunol.2100712","article-title":"Where\u2019s the Beef? 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