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=13

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=<p>In this study, we have investigated the influence of vitamin A on gill barrier function of grass carp (<italic>Ctenopharyngodon idella</italic>) infected with <italic>Flavobacterium columnare.</italic> The fish were fed different concentrations of vitamin A diets for 10 weeks and then infected with <italic>F. columnare</italic> by immersion. We observed that optimal vitamin A significantly prevented gill rot morbidity in fish infected with <italic>F. columnare</italic>. Further investigations revealed that vitamin A boosted the gill immunity by increasing the contents of complements (C3 and C4), activities of acid phosphatase (ACP) and lysozyme, mRNAs of <italic>β-defensin-1, liver-expressed antimicrobial peptide 2A</italic> and <italic>2B (LEAP-2A</italic> and <italic>LEAP-2B)</italic>, <italic>hepcidin</italic>, and anti-inflammatory cytokines like <italic>transforming growth factor β1 (TGF-β1), TGF-β2, interleukin-10 (IL-10),</italic> and <italic>IL-11</italic>. It also enhanced the levels of various related signaling molecules including <italic>inhibitor protein κBα (IκBα), target of rapamycin (TOR),</italic> and <italic>ribosome protein S6 kinase 1 (S6K1)</italic> but downregulated the expression of pro-inflammatory cytokines including <italic>IL-1β, IL-8, tumor necrosis factor α (TNF-α)</italic>, and <italic>interferon γ2 (IFN-γ2)</italic> and related signaling molecules including <italic>nuclear factor κB p65 (NF-κB p65)</italic> (rather than <italic>NF-κB p52), IκB kinase β (IKKβ), IKKγ</italic> (rather than <italic>IKKα), eIF4E-binding protein 1 (4E-BP1),</italic> and <italic>4E-BP2</italic> mRNA levels in fish gills. In addition, dietary vitamin A markedly 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 (GSTs), glutathione peroxidase (GPx), and glutathione reductase (GR) associated with upregulation of <italic>NF-E2-related factor 2 (Nrf2)</italic> mRNAs and downregulation of <italic>Kelch-like-ECH-associated protein (Keap1a)</italic> and <italic>Keap1b</italic> mRNAs. Moreover, vitamin A decreased the mRNAs of different apoptotic mediators [<italic>caspases 8, 9, 3</italic> (rather than 7)] associated with downregulation of signaling molecule <italic>p38 mitogen-activated protein kinase (p38MAPK)</italic> mRNAs in fish gills. Besides, vitamin A promoted tight junction (TJ) complex mRNAs [including <italic>claudin-b, -c, -3, -7, -12, occludin</italic>, and <italic>zonula occludens-1 (ZO-1)</italic>] that have been linked to the downregulation of myosin light chain kinase (MLCK) signaling. Taken together, the current study demonstrated for the first time that vitamin A markedly enhanced gill health associated with immune modulation and physical barrier protection. Based on protecting fish against gill rot morbidity, ACP activity, and against lipid peroxidation, optimum vitamin A concentrations in on-growing grass carp (262–997 g) were found to be 1,991, 2,188, and 2,934 IU/kg diet, respectively.</p>