{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:36:52Z","timestamp":1760060212714,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USDA-ARS bovine project","award":["8042-32000-105-00-D"],"award-info":[{"award-number":["8042-32000-105-00-D"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>One of the most concerning ruminant infections is the parasite Ostertagia ostertagi. Known commonly as the brown stomach worm, it is ingested by grazing cattle where it then progresses its life stages, occupying the host abomasum and then the intestine, causing illness. This results in lower commercial production and at worst, death of young calves. Over time, anthelmintic treatment has become less efficacious against cattle nematodes. As a result, alternative control strategies are needed. Our study looked to elucidate mechanisms underlying attenuation of the host immune response by examining global immune expression in cattle during infection. To this end, four steers were infected with the third stage larvae (L3) of O. ostertagi, then peripheral blood mononuclear cells (PBMCs) were collected weekly for 26 days post-infection (dpi). After sequencing, gene expression was compared between each timepoint. The analyses indicated that the immune responses to Ostertagia are targeted to the parasite\u2019s life stages and mimics anti-viral gene expression. Overall, the results showed that O. ostertagi led to host immune responses characterized by multiple gene ontology and pathway terms indicating that by 26 dpi the host immune system transitions from fighting the parasite to repairing the host intestine.<\/jats:p>","DOI":"10.3390\/biology14081034","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T15:51:02Z","timestamp":1755013862000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Analysis of Peripheral Blood Mononuclear Cells During Ostertagia ostertagi Infection in Cattle Highlights a Generalized Host Immune Reaction"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8377-0032","authenticated-orcid":false,"given":"Damarius S.","family":"Fleming","sequence":"first","affiliation":[{"name":"Animal Parasitic Disease Laboratory, Beltsville Agricultural Research Center, USDA-ARS, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Animal Parasitic Disease Laboratory, Beltsville Agricultural Research Center, USDA-ARS, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9161-167X","authenticated-orcid":false,"given":"Peter","family":"Thompson","sequence":"additional","affiliation":[{"name":"Animal Parasitic Disease Laboratory, Beltsville Agricultural Research Center, USDA-ARS, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethiopia","family":"Beshah","sequence":"additional","affiliation":[{"name":"Animal Parasitic Disease Laboratory, Beltsville Agricultural Research Center, USDA-ARS, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-8981","authenticated-orcid":false,"given":"Wenbin","family":"Tuo","sequence":"additional","affiliation":[{"name":"Animal Parasitic Disease Laboratory, Beltsville Agricultural Research Center, USDA-ARS, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0304-4017(88)90071-4","article-title":"Immunity to Ostertagia ostertagi","volume":"27","author":"Klesius","year":"1988","journal-title":"Vet. Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0304-4017(93)90055-R","article-title":"Pathophysiology of infection with Ostertagia ostertagi in cattle","volume":"46","author":"Fox","year":"1993","journal-title":"Vet. Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.vetpar.2009.02.023","article-title":"The transcriptomes of the cattle parasitic nematode Ostertagia ostartagi","volume":"162","author":"Abubucker","year":"2009","journal-title":"Vet. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1017\/S0022149X00004004","article-title":"The development of the parasitic stages of Ostertagia ostertagi","volume":"43","author":"Rose","year":"1969","journal-title":"J. Helminthol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1128\/IAI.00017-21","article-title":"Ostertagia ostertagi Mediates Early Host Immune Responses via Macrophage and Toll-Like Receptor Pathways","volume":"89","author":"Bakshi","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.vetpar.2010.08.037","article-title":"Localized complement activation in the development of protective immunity against Ostertagia ostertagi infections in cattle","volume":"174","author":"Li","year":"2010","journal-title":"Vet. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.immuni.2018.10.016","article-title":"Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules","volume":"49","author":"Maizels","year":"2018","journal-title":"Immunity"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1017\/S0031182010001241","article-title":"A calcium-activated nucleotidase secreted from Ostertagia ostertagi 4th-stage larvae is a member of the novel salivary apyrases present in blood-feeding arthropods","volume":"138","author":"Zarlenga","year":"2011","journal-title":"Parasitology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Garcia-Campos, A., Correia, C.N., Naranjo-Lucena, A., Garza-Cuartero, L., Farries, G., Browne, J.A., MacHugh, D.E., and Mulcahy, G. (2019). Fasciola hepatica Infection in Cattle: Analyzing Responses of Peripheral Blood Mononuclear Cells (PBMC) Using a Transcriptomics Approach. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02081"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Niedziela, D.A., Naranjo-Lucena, A., Molina-Hernandez, V., Browne, J.A., Martinez-Moreno, A., Perez, J., MacHugh, D.E., and Mulcahy, G. (2021). Timing of Transcriptomic Peripheral Blood Mononuclear Cell Responses of Sheep to Fasciola hepatica Infection Differs From Those of Cattle, Reflecting Different Disease Phenotypes. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.729217"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.ijpara.2014.01.009","article-title":"Ostertagia ostertagi macrophage migration inhibitory factor is present in all developmental stages and may cross-regulate host functions through interaction with the host receptor","volume":"44","author":"Qu","year":"2014","journal-title":"Int. J. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.vetpar.2016.10.011","article-title":"Confirmation of ivermectin resistance in Ostertagia ostertagi in cattle in New Zealand","volume":"229","author":"Waghorn","year":"2016","journal-title":"Vet. Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1051\/parasite\/2020062","article-title":"Increasing importance of anthelmintic resistance in European livestock: Creation and meta-analysis of an open database","volume":"27","author":"Morgan","year":"2020","journal-title":"Parasite"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cvfa.2019.12.001","article-title":"Biology, Epidemiology, Diagnosis, and Management of Anthelmintic Resistance in Gastrointestinal Nematodes of Livestock","volume":"36","author":"Kaplan","year":"2020","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109510","DOI":"10.1016\/j.vetpar.2021.109510","article-title":"Repeated, drug-truncated infections with Ostertagia ostertagi elicit strong humoral and cell-mediated immune responses and confer partial protection in cattle","volume":"296","author":"Tuo","year":"2021","journal-title":"Vet. Parasitol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Avramenko, R.W., Redman, E.M., Lewis, R., Yazwinski, T.A., Wasmuth, J.D., and Gilleard, J.S. (2015). Exploring the Gastrointestinal \u201cNemabiome\u201d: Deep Amplicon Sequencing to Quantify the Species Composition of Parasitic Nematode Communities. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143559"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1093\/bioinformatics\/btx373","article-title":"FQC Dashboard: Integrates FastQC results into a web-based, interactive, and extensible FASTQ quality control tool","volume":"33","author":"Brown","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"W345","DOI":"10.1093\/nar\/gkac247","article-title":"The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2022 update","volume":"50","author":"Galaxy","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-7737-6_6","article-title":"The Ensembl Genome Browser: Strategies for Accessing Eukaryotic Genome Data","volume":"1757","author":"Newman","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D52","DOI":"10.1093\/nar\/gkq1237","article-title":"Entrez Gene: Gene-centered information at NCBI","volume":"39","author":"Maglott","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s12639-018-1023-x","article-title":"Immunity to gastrointestinal nematodes in ruminants: Effector cell mechanisms and cytokines","volume":"42","author":"Hendawy","year":"2018","journal-title":"J. Parasit. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pawlowska, M., Mila-Kierzenkowska, C., Szczegielniak, J., and Wozniak, A. (2023). Oxidative Stress in Parasitic Diseases-Reactive Oxygen Species as Mediators of Interactions between the Host and the Parasites. Antioxidants, 13.","DOI":"10.3390\/antiox13010038"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/pim.12094","article-title":"Analysis of the mucosal immune responses induced by single and trickle infections with the bovine abomasal nematode Ostertagia ostertagi","volume":"36","author":"Mihi","year":"2014","journal-title":"Parasite Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.semcdb.2014.03.004","article-title":"Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and proteolytic processing by a disintegrin and metalloproteinases (ADAM): A regulator of several pathways","volume":"28","author":"Taylor","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1297-9716-42-61","article-title":"Infection with the gastrointestinal nematode Ostertagia ostertagi in cattle affects mucus biosynthesis in the abomasum","volume":"42","author":"Rinaldi","year":"2011","journal-title":"Vet. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ge, Y., Huang, M., and Yao, Y.M. (2022). Efferocytosis and Its Role in Inflammatory Disorders. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.839248"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.molimm.2017.10.012","article-title":"Molecular characterization of the bovine IER3 gene: Down-regulation of IL-8 by blocking NF-kappaB activity mediated by IER3 overexpression in MDBK cells infected with bovine viral diarrhea virus-1","volume":"92","author":"Villalba","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.4110\/in.2018.18.e27","article-title":"Damage-Associated Molecular Patterns in Inflammatory Diseases","volume":"18","author":"Roh","year":"2018","journal-title":"Immune Netw."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ahmed, A.M., Good, B., Hanrahan, J.P., McGettigan, P., Browne, J., Keane, O.M., Bahar, B., Mehta, J., Markey, B., and Lohan, A. (2015). Variation in the Ovine Abomasal Lymph Node Transcriptome between Breeds Known to Differ in Resistance to the Gastrointestinal Nematode. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124823"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"604","DOI":"10.4049\/jimmunol.1701322","article-title":"Cysteine-Reactive Free ISG15 Generates IL-1\u03b2-Producing CD8\u03b1+ Dendritic Cells at the Site of Infection","volume":"201","author":"Napolitano","year":"2018","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Doolan, R., Putananickal, N., Tritten, L., and Bouchery, T. (2023). How to train your myeloid cells: A way forward for helminth vaccines?. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1163364"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.0105-2896.2004.00193.x","article-title":"Immune-mediated regulation of chronic intestinal nematode infection","volume":"201","author":"Hayes","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/09712119.2012.739093","article-title":"Involvement of free radicals in parasitic infestations","volume":"41","year":"2013","journal-title":"J. Appl. Anim. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nri3476","article-title":"Type 2 immunity and wound healing: Evolutionary refinement of adaptive immunity by helminths","volume":"13","author":"Gause","year":"2013","journal-title":"Nat. Rev. Immunol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/8\/1034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:23Z","timestamp":1760034323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/8\/1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["biology14081034"],"URL":"https:\/\/doi.org\/10.3390\/biology14081034","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2025,8,12]]}}}