PMID- 35359991 OWN - NLM STAT- MEDLINE DCOM- 20220408 LR - 20220520 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Novel Insight Into Nutritional Regulation in Enhancement of Immune Status and Mediation of Inflammation Dynamics Integrated Study In Vivo and In Vitro of Teleost Grass Carp (Ctenopharyngodon idella): Administration of Threonine. PG - 770969 LID - 10.3389/fimmu.2022.770969 [doi] LID - 770969 AB - This study aims to investigate the effects of threonine (Thr) on immunoregulation in vivo and in vitro of teleost grass carp (Ctenopharyngodon idella). Juveniles (9.53 +/- 0.02 g) were reared for 8 weeks with respective Thr diet (3.99, 7.70, 10.72, 14.10, 17.96, and 21.66 g/kg) and then challenged with Aeromonas hydrophila for in vivo study. Macrophages isolated from head kidney were treated in vitro for 48 h with L-Thr (0, 0.5, 1.0, 2.0, 4.0, and 8.0 mM) after 6 h of lipopolysaccharide induction. The results showed that, compared with Thr deficiency (3.99 g/kg), the optimal dietary Thr (14.10g/kg) affected the immunocyte activation in the head kidney (HK) and spleen (SP) by downregulating the mRNA expressions of MHC-II and upregulating CD4 (not CD8), and it mediated the innate immune by enhancing the activities of lysozyme (LZ), acid phosphatase content of complement 3 (C3) and C4, increasing the mRNA abundances of hepcidin, liver expressed antimicrobial peptide-2A (LEAP-2A), LEAP-2B, beta-defensin1, downregulating tumor necrosis factor alpha (TNF-alpha), IL-6, IL-1beta, IL-12p35, IL-12p40, IL-17AF1, and IL-17D partly by attenuating RORgamma1 transcriptional factor and nuclear factor kappa B p65 (NF-kappaBp65) signaling cascades [IKKbeta/IkappaBalpha/NF-kappaBp65] and upregulating transforming growth factor beta1 (TGF-beta1), IL-4/13A, -4/13B, IL-10, and IL-22 partly by GATA-3. Besides these, the optimal dietary Thr regulated the adaptive immune by upregulating the mRNAs of immunoglobulin M (IgM) and IgZ (not IgD). Moreover, 2 mM Thr downregulated in vitro the mRNA abundances of colony stimulating factor-1, inducible nitric oxide synthase, mannose receptor 1, matrix metalloproteinase2 (MMP-2), and MMP-9 significantly (P < 0.05), indicating that Thr could attenuate the M1-type macrophages' activation. Moreover, L-Thr downregulated the mRNA transcripts of TNF-alpha, IL-6, and IL-1beta associated with impairing the SOCS1/STAT1 signaling and upregulated IL-10 and TGF-beta1 partly by accentuating the SOCS3/STAT3 pathway. The above-mentioned observations suggested that Thr improved the immune status in the immune organs of fish by enhancing the immune defense and mediating the inflammation process. Finally, based on the immune indices of LZ activity in HK and C3 content in SP, the optimal Thr for immune enhancement in juvenile grass carp (9.53-53.43 g) was determined to be 15.70 g/kg diet (4.85 g/100 g protein) and 14.49 g/kg diet (4.47 g/100 g protein), respectively. CI - Copyright (c) 2022 Dong, Jiang, Wu, Liu, Kuang, Tang, Tang, Zhou and Feng. FAU - Dong, Yu-Wen AU - Dong YW AD - Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China. FAU - Jiang, Wei-Dan AU - Jiang WD AD - Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China. AD - Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China. AD - Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China. FAU - Wu, Pei AU - Wu P AD - Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China. AD - Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China. AD - Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China. FAU - Liu, Yang AU - Liu Y AD - Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China. AD - Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China. AD - Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China. FAU - Kuang, Sheng-Yao AU - Kuang SY AD - Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, China. FAU - Tang, Ling AU - Tang L AD - Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, China. FAU - Tang, Wu-Neng AU - Tang WN AD - Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, China. FAU - Zhou, Xiao-Qiu AU - Zhou XQ AD - Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China. AD - Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China. AD - Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China. FAU - Feng, Lin AU - Feng L AD - Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China. AD - Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China. AD - Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China. LA - eng PT - Journal Article DEP - 20220314 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 2ZD004190S (Threonine) SB - IM MH - Animals MH - *Carps MH - *Fish Diseases MH - *Gram-Negative Bacterial Infections/veterinary MH - Inflammation MH - Interleukin-10 MH - Interleukin-6 MH - RNA, Messenger MH - Threonine MH - Transforming Growth Factor beta1 MH - Tumor Necrosis Factor-alpha PMC - PMC8963965 OTO - NOTNLM OT - immune status OT - in vivo and in vitro OT - inflammation OT - juvenile grass carp OT - threonine COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/04/02 06:00 MHDA- 2022/04/09 06:00 PMCR- 2022/01/01 CRDT- 2022/04/01 05:15 PHST- 2021/09/05 00:00 [received] PHST- 2022/02/09 00:00 [accepted] PHST- 2022/04/01 05:15 [entrez] PHST- 2022/04/02 06:00 [pubmed] PHST- 2022/04/09 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.770969 [doi] PST - epublish SO - Front Immunol. 2022 Mar 14;13:770969. doi: 10.3389/fimmu.2022.770969. eCollection 2022.