AUTHOR=Jiang Wei-Dan , Zhang Li , Feng Lin , Wu Pei , Liu Yang , Kuang Sheng-Yao , Li Shu-Wei , Tang Ling , Mi Hai-Feng , Zhang Lu , Zhou Xiao-Qiu TITLE=New Insight on the Immune Modulation and Physical Barrier Protection Caused by Vitamin A in Fish Gills Infected With Flavobacterium columnare JOURNAL=Frontiers in Immunology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.833455 DOI=10.3389/fimmu.2022.833455 ISSN=1664-3224 ABSTRACT=Here, we investigated the influence of vitamin A on gill barrier function of grass carp (Ctenopharyngodon idella) infected with Flavobacterium columnare. Fish intake different vitamin A concentration diets for 10-weeks, and then infected with F. columnare by immersion. We observed that optimal vitamin A prevented gill rot morbidity in fish infected by F. columnare. We further observed that vitamin A boost the gill immunity by increasing contents of complements (C3 and C4), activities of phosphatase (ACP) and lysozyme (LA), mRNAs of β-defensin-1, liver-expressed antimicrobial peptide 2A and 2B (LEAP-2A and -2B), hepcidin, anti-inflammatory cytokines like transforming growth factor β1 (TGF-β1) and TGF-β2, interleukin-10 (IL-10), IL-11, and related signaling molecules including inhibitor protein κBα (IκBα), target of rapamycin (TOR) and ribosome protein S6 kinase 1 (S6K1), whereas down-regulated pro-inflammatory cytokines including IL-1β and IL-8, tumor necrosis factor α (TNF-α), interferon γ2 (IFN-γ2), and related signaling molecules nuclear factor κB p65 (NF-κB p65) (rather than NF-κB p52), IκB kinase β (IKKβ) and IKKγ (rather than IKKα), eIF4E-binding protein 1 (4E-BP1) and 4E-BP2 mRNA levels in fish gills. In addition, dietary vitamin A lowered the concentrations of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC), increased both the activities and mRNAs of copper/zinc superoxide dismutase (Cu/ZnSOD), MnSOD, glutathione transferases (GST), glutathione peroxidase (GPx) as well as glutathione reductase (GR) associated with up-regulation of NF-E2-related factor 2 (Nrf2) mRNAs and down-regulation of kelch-like-ECH-associated protein (keap1a) and keap1b mRNAs. Meanwhile, vitamin A decreased the mRNAs of the apoptosis signaling [caspase-8, -9, -3 (rather than -7)] associated with down-regulation of signaling molecule p38 mitogen-activated protein kinase (p38MAPK) mRNAs in fish gills. Besides, vitamin A promoted TJ complexs mRNAs [including claudin-b, -c, -3, -7, -12, occludin and zonula occludens-1 (ZO-1)] which linked to the down-regulation of MLCK signaling. Taken together, current study firstly demonstrated that vitamin A enhanced gill health associated with immune modulation and physical barrier protection. Based on protecting fish against the gill rot morbidity, ACP activity and against the lipid peroxidation, optimum vitamin A in on-growing grass carp (262-997 g) were evaluated to be 1991, 2188 and 2934 IU/kg diet, respectively.