{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:05:59Z","timestamp":1789707959944,"version":"4.0.1"},"reference-count":64,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANID","award":["11240684"],"award-info":[{"award-number":["11240684"]}],"id":[{"id":"https:\/\/ror.org\/05btm5233","id-type":"ROR","asserted-by":"crossref"}]},{"award":["11240684"],"award-info":[{"award-number":["11240684"]}],"id":[{"id":"https:\/\/ror.org\/05btm5233","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Tenacibaculosis, primarily caused by Tenacibaculum dicentrarchi in Chile, is now the second leading infectious cause of mortality in Chilean Atlantic salmon (Salmo salar) farming, yet the host immune response remains uncharacterized. Here, we combined in vitro and in vivo approaches to characterize the immunopathological interaction between Atlantic salmon and a Chilean T. dicentrarchi isolate. Primary head kidney macrophages stimulated with live bacteria showed early and sustained upregulation of tnf\u03b1, il1\u03b2, and il8 (4\u201324 h), followed by late induction of inos at 24 h, consistent with a classical M1-like proinflammatory profile. In parallel, il10 was robustly upregulated, while M2 marker arg was downregulated, reflecting balanced immunoregulation with active suppression of alternative activation. Production of TNF-\u03b1 and IL-10 proteins was confirmed by immunofluorescence. An immersion challenge validated pathogenic relevance, yielding 32.4% cumulative mortality, with peak deaths at day 4 and a clinical course matching field outbreaks, including frayed fins, skin ulcers, mouth damage, and hemorrhage, with partial lesion resolution by day 28. Together, these results provide the first integrated in vitro\u2013in vivo characterization of the Atlantic salmon response to T. dicentrarchi, combining cellular immune response profiling with experimental disease progression, and establishing a reproducible approach that captures both acute and recovery phases of disease, supporting future vaccine and therapeutic development against tenacibaculosis.<\/jats:p>","DOI":"10.3390\/ani16182908","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:58:59Z","timestamp":1789545539000},"page":"2908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of the Immune Response of Atlantic Salmon to Tenacibaculum dicentrarchi Using In Vivo and In Vitro Approaches"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0807-4234","authenticated-orcid":false,"given":"D\u00e9bora","family":"Torrealba","sequence":"first","affiliation":[{"name":"Laborarorio de Nanobiotecnolog\u00eda e Inmunolog\u00eda Marina, Instituto de Ciencias de la Ingenier\u00eda, Universidad de O\u2019Higgins, Avenida Libertador Bernardo O\u2019Higgins 611, Rancagua 2841959, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-3569","authenticated-orcid":false,"given":"Cristobal","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Programa de Doctorado en Biotecnolog\u00eda, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2373223, Chile"},{"name":"Programa de Doctorado en Biotecnolog\u00eda, Universidad T\u00e9cnica Federico Santa Mar\u00eda, Valpara\u00edso 2373223, Chile"},{"name":"Centro Nacional de Acuicultura e Investigaciones Marinas, CENAIM, Escuela Superior Polit\u00e9cnica del Litoral, ESPOL, Polytechnic University, Campus Gustavo Galindo Km. 30.5 V\u00eda Perimetral, Guayaquil P.O. Box 09-01-5863, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Paula","family":"Valenzuela-Avil\u00e9s","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Gen\u00f3mica Aplicada, Escuela de Ciencias del Mar, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Avenida Universidad 330, Valpara\u00edso 2373223, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-8726","authenticated-orcid":false,"given":"Jos\u00e9","family":"Gallardo-Matus","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Gen\u00f3mica Aplicada, Escuela de Ciencias del Mar, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Avenida Universidad 330, Valpara\u00edso 2373223, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Luis","family":"Mercado","sequence":"additional","affiliation":[{"name":"Grupo de Marcadores Inmunol\u00f3gicos en Organismos Acu\u00e1ticos, Instituto de Biolog\u00eda, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Avenida Universidad 330, Valpara\u00edso 2373223, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0100-2190","authenticated-orcid":false,"given":"Marcos","family":"Mancilla","sequence":"additional","affiliation":[{"name":"ADL Diagnostic Chile, Puerto Montt 5480000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1099\/ijs.0.025122-0","article-title":"Tenacibaculum dicentrarchi sp. nov., a marine bacterium of the family Flavobacteriaceae isolated from European sea bass","volume":"62","author":"Gijon","year":"2012","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/tbed.12464","article-title":"Isolation, Characterization and Virulence Potential of Tenacibaculum dicentrarchi in Salmonid Cultures in Chile","volume":"63","author":"Irgang","year":"2016","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5503","DOI":"10.1128\/AEM.01177-14","article-title":"Multilocus sequence analysis of the marine bacterial genus Tenacibaculum suggests parallel evolution of fish pathogenicity and endemic colonization of aquaculture systems","volume":"80","author":"Habib","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1111\/jfd.12643","article-title":"First identification and characterization of Tenacibaculum dicentrarchi isolated from Chilean red conger eel (Genypterus chilensis, Guichenot 1848)","volume":"40","author":"Irgang","year":"2017","journal-title":"J. Fish Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e70039","DOI":"10.1111\/jfd.70039","article-title":"First Report of Tenacibaculum dicentrarchi in Diseased Palm Ruff (Seriolella violacea, Guichenot 1848) from an Experimental Culture in Chile","volume":"49","author":"Oliva","year":"2026","journal-title":"J. Fish Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.fsi.2019.12.093","article-title":"Chilean aquaculture and the new challenges: Pathogens, immune response, vaccination and fish diversification","volume":"98","author":"Montero","year":"2020","journal-title":"Fish Shellfish Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"734267","DOI":"10.1016\/j.aquaculture.2019.734267","article-title":"Biofilm development and cell viability: An undervalued mechanism in the persistence of the fish pathogen Tenacibaculum maritimum","volume":"511","author":"Levipan","year":"2019","journal-title":"Aquaculture"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e14088","DOI":"10.1111\/jfd.14088","article-title":"Experimental Challenge of Chinook Salmon (Oncorhynchus tshawytscha) with Tenacibaculum maritimum and Tenacibaculum dicentrarchi Fulfils Koch\u2019s Postulates","volume":"48","author":"Kumanan","year":"2025","journal-title":"J. Fish Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/jfd.12982","article-title":"An outbreak of acute disease and mortality in Atlantic salmon (Salmo salar) post-smolts in Norway caused by Tenacibaculum dicentrarchi","volume":"42","author":"Klakegg","year":"2019","journal-title":"J. Fish Dis."},{"key":"ref_10","unstructured":"SERNAPESCA (2018). Informe Sanitario Salmonicultura en Centros Marinos 2018, Servicio Nacional de Pesca y Acuicultura."},{"key":"ref_11","unstructured":"SERNAPESCA (2025). Informe con Antecedentes Sanitarios de Agua Dulce y Agua de Mar, Servicio Nacional de Pesca y Acuicultura."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/08997659.2017.1339643","article-title":"Primary Isolation and Characterization of Tenacibaculum maritimum from Chilean Atlantic Salmon Mortalities Associated with a Pseudochattonella spp. Algal Bloom","volume":"29","author":"Apablaza","year":"2017","journal-title":"J. Aquat. Anim. Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1111\/jfd.13466","article-title":"First report and characterization of Tenacibaculum maritimum isolates recovered from rainbow trout (Oncorhynchus mykiss) farmed in Chile","volume":"44","author":"Valdes","year":"2021","journal-title":"J. Fish Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/jfd.13213","article-title":"New salmonid hosts for Tenacibaculum species: Expansion of tenacibaculosis in Chilean aquaculture","volume":"43","author":"Collarte","year":"2020","journal-title":"J. Fish Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e14122","DOI":"10.1111\/jfd.14122","article-title":"O-Antigen Gene Cluster Reveals Genomic Variation in Chilean Tenacibaculum dicentrarchi Through Multiplex PCR-Based Genotyping Scheme","volume":"48","author":"Lopez","year":"2025","journal-title":"J. Fish Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/jfd.13577","article-title":"Tenacibaculosis in Norwegian Atlantic salmon (Salmo salar) cage-farmed in cold sea water is primarily associated with Tenacibaculum finnmarkense genomovar finnmarkense","volume":"45","author":"Spilsberg","year":"2022","journal-title":"J. Fish Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e70144","DOI":"10.1111\/jfd.70144","article-title":"Cohabitation Challenge Demonstrates Minimal Transmission of Tenacibaculosis From Atlantic Salmon (Salmo salar L.) to Coho Salmon (Oncorhynchus kisutch W.)","volume":"49","author":"Nowlan","year":"2026","journal-title":"J. Fish Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Smage, S.B., Brevik, O.J., Frisch, K., Watanabe, K., Duesund, H., and Nylund, A. (2017). Concurrent jellyfish blooms and tenacibaculosis outbreaks in Northern Norwegian Atlantic salmon (Salmo salar) farms. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187476"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/jfd.13604","article-title":"Evaluation of the in vitro susceptibility of Tenacibaculum dicentrarchi to tiamulin using minimum inhibitory concentration tests","volume":"45","author":"Irgang","year":"2022","journal-title":"J. Fish Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108747","DOI":"10.1016\/j.fsi.2023.108747","article-title":"Healthy and infected Atlantic salmon (Salmo salar) skin-mucus response to Tenacibaculum dicentrarchi under in vitro conditions","volume":"136","author":"Irgang","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e14157","DOI":"10.1111\/jfd.14157","article-title":"Skin-Mucus Prokaryote Community of Atlantic Salmon (Salmo salar) in Response to Bath Challenge With Tenacibaculum dicentrarchi","volume":"48","author":"Tralma","year":"2025","journal-title":"J. Fish Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s42523-021-00096-2","article-title":"Salmon gut microbiota correlates with disease infection status: Potential for monitoring health in farmed animals","volume":"3","author":"Bozzi","year":"2021","journal-title":"Anim. Microbiome"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nowlan, J.P., Britney, S.R., Lumsden, J.S., and Russell, S. (2021). Experimental induction of tenacibaculosis in atlantic salmon (Salmo salar l.) using Tenacibaculum maritimum, T dicentrarchi, and T. finnmarkense. Pathogens, 10.","DOI":"10.3390\/pathogens10111439"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ferreira, I.A., Peixoto, D., Losada, A.P., Quiroga, M.I., do Vale, A., and Costas, B. (2023). Early innate immune responses in European sea bass (Dicentrarchus labrax L.) following Tenacibaculum maritimum infection. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1254677"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Carvalho, I., Peixoto, D., Ferreira, I., Robledo, D., Ramos-Pinto, L., Silva, R.M., Goncalves, J.F., Machado, M., Tafalla, C., and Costas, B. (2025). Exploring the effects of dietary methionine supplementation on European seabass mucosal immune responses against Tenacibaculum maritimum. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1513516"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.fsi.2019.02.015","article-title":"Mucosal and systemic immune responses in Senegalese sole (Solea senegalensis Kaup) bath challenged with Tenacibaculum maritimum: A time-course study","volume":"87","author":"Guardiola","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Buchmann, K., and Secombes, C. (2022). Mucosal Immunity in Fish. Principles of Fish Immunology. From Cells and Molecules to Host Protection, Springer.","DOI":"10.1007\/978-3-030-85420-1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.fsi.2014.01.001","article-title":"Comparative skin mucus and serum humoral defence mechanisms in the teleost gilthead seabream (Sparus aurata)","volume":"36","author":"Guardiola","year":"2014","journal-title":"Fish Shellfish Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/j.1444-2906.2005.01000.x","article-title":"Immune response of sea bass Dicentrarchus labrax to Tenacibaculum maritimum antigens","volume":"71","author":"Salati","year":"2005","journal-title":"Fish. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109943","DOI":"10.1016\/j.fsi.2024.109943","article-title":"Outer membrane vesicles (OMVs) from Tenacibaculum maritimum as a potential vaccine against fish tenacibaculosis","volume":"154","author":"Escribano","year":"2024","journal-title":"Fish Shellfish Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13888","DOI":"10.1111\/jfd.13888","article-title":"Tenacibaculum dicentrarchi produce outer membrane vesicles (OMV) that are associated with the cytotoxic effect in rainbow trout head kidney macrophages","volume":"47","year":"2024","journal-title":"J. Fish Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sepulveda, D., Bohle, H., Labra, A., Grothusen, H., and Marshall, S. (2013). Design and evaluation of a unique RT-qPCR assay for diagnostic quality control assessment that is applicable to pathogen detection in three species of salmonid fish. BMC Vet. Res., 9.","DOI":"10.1186\/1746-6148-9-183"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.molimm.2005.07.009","article-title":"Expression profiling and validation of reference gene candidates in immune relevant tissues and cells from Atlantic salmon (Salmo salar L.)","volume":"43","author":"Ingerslev","year":"2006","journal-title":"Mol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Salinas-Parra, N., Pombett, Y., Stambuk, F., Ilufi, M., Ram\u00edrez-Cepeda, F., Valenzuela, C.A., Soto, C., Gallardo-Matus, J., and Mercado, L. (2026). Comparative Gill Transcriptomics Reveals Unresolved Inflammation Under Chronic Hypoxia and Molecular Plasticity During Cyclic Hypoxia in Salmo salar. Animals, 16.","DOI":"10.2139\/ssrn.6504684"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/jfd.12767","article-title":"PCR procedure for detecting the fish pathogen Tenacibaculum dicentrarchi","volume":"41","author":"Irgang","year":"2018","journal-title":"J. Fish Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Alvarez, C.A., Santana, P.A., Salinas-Parra, N., Beltran, D., Guzman, F., Vega, B., Acosta, F., and Mercado, L. (2022). Immune Modulation Ability of Hepcidin from Teleost Fish. Animals, 12.","DOI":"10.3390\/ani12121586"},{"key":"ref_38","first-page":"21","article-title":"Immunological strategy for detecting the pro-inflammatory cytokine TNF-alpha in salmonids","volume":"15","author":"Rojas","year":"2012","journal-title":"Electron. J. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08997659.2012.668507","article-title":"Pathology of ocular lesions associated with gas supersaturation in white seabass","volume":"24","author":"Smiley","year":"2012","journal-title":"J. Aquat. Anim. Health"},{"key":"ref_40","unstructured":"SERNAPESCA (2024). Informe con Antecedentes Sanitarios de Agua de mar y Agua Dulce A\u00f1o 2023, Servicio Nacional de Pesca y Acuicultura."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"lxae049","DOI":"10.1093\/jambio\/lxae049","article-title":"The use of salmonid epithelial cells to characterize the toxicity of Tenacibaculum maritimum soluble extracellular products","volume":"135","author":"Michnik","year":"2024","journal-title":"J. Appl. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"110466","DOI":"10.1016\/j.fsi.2025.110466","article-title":"Atlantic salmon scale explants in bacteria-host interaction studies: In vitro challenge model","volume":"165","author":"Krasnov","year":"2025","journal-title":"Fish Shellfish Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"200157","DOI":"10.1016\/j.cirep.2024.200157","article-title":"Development and use of a Chinook salmon spleen stromal-like cell line to study the cellular immune response to Vibrio anguillarum","volume":"7","author":"Semple","year":"2024","journal-title":"Comp. Immunol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.dci.2008.09.012","article-title":"Expression profiles of cytokines released in intestinal epithelial cells of the rainbow trout, Oncorhynchus mykiss, in response to bacterial infection","volume":"33","author":"Komatsu","year":"2009","journal-title":"Dev. Comp. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.fsi.2016.09.053","article-title":"Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss)","volume":"58","author":"Kutyrev","year":"2016","journal-title":"Fish Shellfish Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Swain, B., and Miryala, K.R. (2025). NOD-like receptors in fish: Evolution, structure, immune signaling, and targeting for aquaculture vaccine adjuvants. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1665071"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.fsi.2018.04.016","article-title":"Under control: The innate immunity of fish from the inhibitors\u2019 perspective","volume":"77","author":"Rebl","year":"2018","journal-title":"Fish Shellfish Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1046\/j.1365-2567.2000.00914.x","article-title":"The gills are an important site of iNOS expression in rainbow trout Oncorhynchus mykiss after challenge with the Gram-positive","volume":"99","author":"Ward","year":"2000","journal-title":"Immunology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Diaz, R., Troncoso, J., Jakob, E., and Skugor, S. (2021). Limiting access to iron decreases infection of Atlantic salmon SHK-1 cells with bacterium Piscirickettsia salmonis. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-021-02853-6"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0145-305X(98)00036-6","article-title":"Expression of an inducible nitric oxide synthase gene in rainbow trout Oncorhynchus mykiss","volume":"23","author":"Laing","year":"1999","journal-title":"Dev. Comp. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.gene.2018.03.018","article-title":"Lipopolysaccharide causes NFkB-mediated induction of inducible nitric oxide synthase gene and more production of nitric oxide in air-breathing catfish, Clarias magur (Hamilton)","volume":"658","author":"Choudhury","year":"2018","journal-title":"Gene"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109469","DOI":"10.1016\/j.fsi.2024.109469","article-title":"Extracellular ATP- and adenosine-mediated purinergic signaling modulates inducible nitric oxide synthase (iNOS) gene expression, enzyme activity and nitric oxide production in common carp (Cyprinus carpio) head kidney macrophages","volume":"147","author":"Li","year":"2024","journal-title":"Fish Shellfish Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"L175","DOI":"10.1152\/ajplung.00295.2012","article-title":"Induction of nitric oxide synthase expression by lipopolysaccharide is mediated by calcium-dependent PKCalpha-beta1 in alveolar epithelial cells","volume":"305","author":"Boncoeur","year":"2013","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10917","DOI":"10.18632\/oncotarget.7295","article-title":"First in-depth analysis of the novel Th2-type cytokines in salmonid fish reveals distinct patterns of expression and modulation but overlapping bioactivities","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.fsi.2019.03.075","article-title":"Rainbow trout (Oncorhynchus mykiss) urea cycle and polyamine synthesis gene families show dynamic expression responses to inflammation","volume":"89","author":"Clark","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.molimm.2015.09.026","article-title":"Polarization of immune responses in fish: The \u2018macrophages first\u2019 point of view","volume":"69","author":"Wiegertjes","year":"2016","journal-title":"Mol. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Segner, H., Rehberger, K., Bailey, C., and Bo, J. (2022). Assessing Fish Immunotoxicity by Means of In Vitro Assays: Are We There Yet?. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.835767"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1023\/A:1026304212673","article-title":"Applications and needs of fish and shellfish cell culture for disease control in aquaculture","volume":"13","author":"Villena","year":"2003","journal-title":"Rev. Fish Biol. Fish."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"100096","DOI":"10.1016\/j.fsirep.2023.100096","article-title":"Dynamics of co-infection in fish: A review of pathogen-host interaction and clinical outcome","volume":"4","author":"Okon","year":"2023","journal-title":"Fish Shellfish Immunol. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"110625","DOI":"10.1016\/j.fsi.2025.110625","article-title":"Cell lines and primary cultures uses for vaccine development for bacterial pathogens of fish: A systematic review","volume":"166","author":"Torrealba","year":"2025","journal-title":"Fish Shellfish Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e70013","DOI":"10.1111\/jfd.70013","article-title":"Efficacy of a Vaccine for Atlantic Salmon (Salmo salar) Using a Tenacibaculum dicentrarchi Strain Cultured Under Iron-Limited Conditions","volume":"49","author":"Irgang","year":"2026","journal-title":"J. Fish Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.micpath.2013.09.003","article-title":"Tenacibaculum maritimum infection: Pathology and immunohistochemistry in experimentally challenged turbot (Psetta maxima L.)","volume":"65","author":"Failde","year":"2013","journal-title":"Microb. Pathog."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1365-2761.2012.01360.x","article-title":"Morphopathological features of a severe ulcerative disease outbreak associated with Tenacibaculum maritimum in cultivated sole, Solea senegalensis (L.)","volume":"35","author":"Vilar","year":"2012","journal-title":"J. Fish Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3354\/dao02219","article-title":"Experimentally induced marine flexibacteriosis in Atlantic salmon smolts Salmo salar. I. Pathogenicity","volume":"91","author":"Gelderen","year":"2010","journal-title":"Dis. Aquat. 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