Abstract
Several nutrients are crucial in enhancing the immune system and preserving the structural integrity of bodily tissue barriers. Vitamin D (VD) and zinc (Zn) have received considerable interest due to their immunomodulatory properties and ability to enhance the body’s immune defenses. Due to their antiviral, anti-inflammatory, antioxidative, and immunomodulatory properties, the two nutritional powerhouses VD and Zn are crucial for innate and adaptive immunity. As observed with COVID-19, deficiencies in these micronutrients impair immune responses, increasing susceptibility to viral infections and severe disease. Ensuring an adequate intake of VD and Zn emerges as a promising strategy for fortifying the immune system. Ongoing clinical trials are actively investigating their potential therapeutic advantages. Beyond the immediate context of the pandemic, these micronutrients offer valuable tools for enhancing immunity and overall well-being, especially in the face of future viral threats. This analysis emphasizes the enduring significance of VD and Zn as both treatment and preventive measures against potential viral challenges beyond the current health crisis. The overview delves into the immunomodulatory potential of VD and Zn in combating viral infections, with particular attention to their effects on animals. It provides a comprehensive summary of current research findings regarding their individual and synergistic impacts on immune function, underlining their potential in treating and preventing viral infections. Overall, this overview underscores the need for further research to understand how VD and Zn can modulate the immune response in combatting viral diseases in animals.
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No datasets were generated or analysed during the current study.
References
Siddiqui M, Manansala JS et al (2020) Immune modulatory effects of vitamin D on viral infections. Nutrients 12(9):2879
Cashman KD, Dowling KG et al (2016) Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr 103(4):1033–1044
Childs CE, Calder PC, Miles EA (2019) Diet and Immune function. MDPI, p 1933
Wu D, Lewis ED, Pae M, Meydani SN (2019) Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Front Immunol 9:3160
Ferrara F, De Rosa F, Vitiello A (2020) The central role of clinical nutrition in Covid-19 patients during and after hospitalization in intensive care unit. SN Compr Clin Med 2(8):1064–1068
Infusino F, Marazzato M et al (2020) Diet supplementation, probiotics, and nutraceuticals in Sars-Cov-2 infection: a scoping review. Nutrients 12(6):1718
Jaggers GK, Watkins BA, Rodriguez RL (2020) Covid-19: repositioning nutrition research for the next pandemic. Nutr Res (New York, NY) 81:1
Johnston CS, Barkyoumb GM, Schumacher SS (2014) Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: a randomized controlled trial. Nutrients 6(7):2572–2583
Lassi ZS, Moin A, Bhutta ZA (2016) Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 12(12):CD005978. https://doi.org/10.1002/14651858.CD005978.pub3
Sánchez J, Villada OA et al (2014) Effect of zinc amino acid chelate and zinc sulfate in the incidence of respiratory infection and diarrhea among preschool children in child daycare centers. Biomedica 34(1):79–91
Ahsan N, Imran M et al (2023) Mechanistic insight into the role of vitamin D and zinc in modulating immunity against Covid-19: a view from an immunological standpoint. Biol Trace Elem Res 201:1–15
Cure E, Cure MC (2020) Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during Covid-19 pandemic. Diabetes Metab Syndr 14(4):349–350
Gombart AF, Pierre A, Maggini S (2020) A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nutrients 12(1):236
Jovic TH, Ali SR et al (2020) Could Vitamins help in the fight against Covid-19? Nutrients 12(9):2550
Messina G, Polito R et al (2020) Functional role of dietary intervention to improve the outcome of Covid-19: a hypothesis of work. Int J Mol Sci 21(9):3104
Castro LCGD (2011) O Sistema Endocrinológico Vitamina D. Arquivos Brasileiros de Endocrinol Metabol 55:566–575
Borel P, Caillaud D, Cano N (2015) Vitamin D bioavailability: state of the art. Crit Rev Food Sci Nutr 55(9):1193–1205
Göring H (2018) Vitamin D in nature: a product of synthesis and/or degradation of cell membrane components. Biochem Mosc 83:1350–1357
Rao DS, Raghuramulu N (1998) Vitamin D metabolism in tilapia (Oreochromis Mossambicus). Comp Biochem Physiol C: Pharmacol Toxicol Endocrinol 120(1):145–149
Takeuchi A, Okano T, Kobayashi T (1991) The existence of 25-hydroxyvitamin D3–1α-hydroxylase in the liver of carp and bastard halibut. Life Sci 48(3):275–282
Arora J, Wang J et al (2022) Novel Insight into the role of the vitamin D receptor in the development and function of the immune system. J Steroid Biochem Mol Biol 219:106084
Voltan G, Cannito M et al (2023) Vitamin D: an overview of gene regulation, ranging from metabolism to genomic effects. Genes 14(9):1691
Bikle DD (2022) Vitamin D regulation of immune function during Covid-19. Rev Endocr Metab Disord 23(2):279–285
Pérez-Ferro M, Romero-Bueno F et al (2019) A subgroup of lupus patients with nephritis, innate T cell activation and low vitamin D is identified by the enhancement of circulating Mhc class I-related chain A. Clin Exp Immunol 196(3):336–344
Komisarenko YI, Bobryk MI (2018) Vitamin D deficiency and immune disorders in combined endocrine pathology. Front Endocrinol (Lausanne) 9:600
Oh S, Chun S et al (2021) Vitamin D and exercise are major determinants of natural killer cell activity, which is age-and gender-specific. Front Immunol 12:594356
Lagishetty V, Misharin AV et al (2010) Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis. Endocrinology 151(6):2423–2432
Grad R (2004) Cod and the consumptive: a brief history of cod-liver oil in the treatment of pulmonary tuberculosis. Pharm Hist 46(3):106–120
Scherberich J, Kellermeyer M, Ried C, Hartinger A (2005) 1-Alpha-calcidol modulates major human monocyte antigens and Toll-like receptors Tlr 2 and Tlr4 in vitro. Eur J Med Res 10(4):179–182
Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252
Aranow C (2011) Vitamin D and the immune system. J Investig Med 59(6):881–886
Mora JR, Iwata M, Von Andrian UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8(9):685–698
Penna G, Amuchastegui S et al (2007) 1, 25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells. J Immunol 178(1):145–153
Veldman CM, Cantorna MT, DeLuca HF (2000) Expression of 1, 25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys 374(2):334–338
Iruretagoyena MI, Wiesendanger M, Kalergis AM (2006) The dendritic cell-T cell synapse as a determinant of autoimmune pathogenesis. Curr Pharm Des 12(2):131–147
Gordon JR, Ma Y et al (2014) Regulatory dendritic cells for immunotherapy in immunologic diseases. Front Immunol 5:7
Adorini L, Amuchastegui S et al (2007) Vitamin D receptor agonists as anti-inflammatory agents. Expert Rev Clin Immunol 3(4):477–489
Griffin MD, Lutz W et al (2001) Dendritic cell modulation by 1α, 25 dihydroxyvitamin D3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci 98(12):6800–6805
Penna G, Amuchastegui S, Laverny G, Adorini L (2007) Vitamin D receptor agonists in the treatment of autoimmune diseases: selective targeting of myeloid but not plasmacytoid dendritic cells. J Bone Miner Res 22(S2):V69–V73
Warwick T, Schulz MH et al (2021) A hierarchical regulatory network analysis of the vitamin D induced transcriptome reveals novel regulators and complete Vdr dependency in monocytes. Sci Rep 11(1):6518
Gombart AF, Borregaard N, Koeffler HP (2005) Human cathelicidin antimicrobial peptide (Camp) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1, 25-dihydroxyvitamin D3. FASEB J 19(9):1067–1077
Kamen DL, Tangpricha V (2010) Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med 88:441–450
Kong J, Zhang Z et al (2008) Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol-Gastrointest Liver Physiol 294(1):G208–G216
Liu PT, Krutzik SR, Modlin RL (2007) Therapeutic implications of the Tlr and Vdr partnership. Trends Mol Med 13(3):117–124
Waterhouse JC, Perez TH, Albert PJ (2009) Reversing bacteria-induced vitamin D receptor dysfunction is key to autoimmune disease. Ann N Y Acad Sci 1173(1):757–765
Wang Z, Yang H et al (2019) Effects of vitamin D receptor on mucosal barrier proteins in colon cells under hypoxic environment. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 41(4):506–511
Lee PC, Hsieh YC et al (2021) Active vitamin D3 treatment attenuated bacterial translocation via improving intestinal barriers in cirrhotic rats. Mol Nutr Food Res 65(3):2000937
Fujita H, Sugimoto K et al (2008) Tight junction proteins claudin-2 and-12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell 19(5):1912–1921
Zhang Y-g, Wu S et al (2015) Tight junction Cldn2 gene is a direct target of the vitamin D receptor. Sci Rep 5(1):10642
Blaney GP, Albert PJ, Proal AD (2009) Vitamin D metabolites as clinical markers in autoimmune and chronic disease. Ann N Y Acad Sci 1173(1):384–390
Gocek E, Studzinski GP (2009) Vitamin D and differentiation in cancer. Crit Rev Clin Lab Sci 46(4):190–209
Heaney RP (2008) Vitamin D in health and disease. Clin J Am Soc Nephrol: CJASN 3(5):1535
Corridoni D, Arseneau KO, Cifone MG, Cominelli F (2014) The dual role of nod-like receptors in mucosal innate immunity and chronic intestinal inflammation. Front Immunol 5:317
Ivanov AI, Nusrat A, Parkos CA (2004) The epithelium in inflammatory bowel disease: potential role of endocytosis of junctional proteins in barrier disruption. in Inflammatory Bowel Disease: Crossroads of Microbes, Epithelium and Immune Systems: Novartis Foundation Symposium 263. Wiley Online Library
Yamada A, Arakaki R et al (2016) Role of regulatory T cell in the pathogenesis of inflammatory bowel disease. World J Gastroenterol 22(7):2195
Azad AK, Sadee W, Schlesinger LS (2012) Innate immune gene polymorphisms in tuberculosis. Infect Immun 80(10):3343–3359
Dresner-Pollak R, Ackerman Z et al (2004) The Bsm I vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients. Genet Test 8(4):417–420
Eloranta JJ, Wenger C et al (2011) Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease. Pharmacogenet Genomics 21(9):559–564
Lee YH, Song GG (2012) Pathway analysis of a genome-wide association study of ileal Crohn’s disease. DNA Cell Biol 31(10):1549–1554
Simmons J, Mullighan C, Welsh K, Jewell D (2000) Vitamin D receptor gene polymorphism: association with Crohn’s disease susceptibility. Gut 47(2):211
Abreu M, Kantorovich V et al (2004) Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn’s disease patients with elevated 1, 25-dihydroxyvitamin D and low bone mineral density. Gut 53(8):1129
Bakke D, Sun J (2018) Ancient nuclear receptor Vdr with new functions: microbiome and inflammation. Inflamm Bowel Dis 24(6):1149–1154
Lim W-C, Hanauer SB, Li YC (2005) Mechanisms of disease: vitamin D and inflammatory bowel disease. Nat Clin Pract Gastroenterol Hepatol 2(7):308–315
Sentongo TA, Semaeo EJ et al (2002) Vitamin D status in children, adolescents, and young adults with Crohn disease. Am J Clin Nutr 76(5):1077–1081
Stio M, Martinesi M et al (2006) Interaction among vitamin D3 analogue Kh 1060, Tnf-Α, and vitamin D receptor protein in peripheral blood mononuclear cells of inflammatory bowel disease patients. Int Immunopharmacol 6(7):1083–1092
Cantorna MT, Zhu Y, Froicu M, Wittke A (2004) Vitamin D status, 1, 25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 80(6):1717S-1720S
Cantorna MT (2006) Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol 92(1):60–64
Kong J, Qiao G et al (2008) Targeted vitamin D receptor expression in juxtaglomerular cells suppresses renin expression independent of parathyroid hormone and calcium. Kidney Int 74(12):1577–1581
Wu S, Zhang YG, Lu R, Xia Y, Zhou Z, Petrof EO, Claud EC, Chang EB, Carmeliet G, Sun J (2014) Tu1753 Intestinal Epithelial Vitamin D Receptor Deletion Leads to Defective Autophagy and Dysbiosis in Colitis. Gastroenterology 5(146):S–834.
Zhang Y-g, Lu R et al (2019) Lack of vitamin D receptor leads to hyperfunction of claudin-2 in intestinal inflammatory responses. Inflamm Bowel Dis 25(1):97–110
Ishii M, Yamaguchi Y et al (2017) Transgenic mice overexpressing vitamin D receptor (Vdr) show anti-inflammatory effects in lung tissues. Inflammation 40(6):2012–2019
Chen S, Sims GP et al (2007) Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179(3):1634–1647
Rolf L, Muris AH, Hupperts R, Damoiseaux J (2014) Vitamin D effects on B cell function in autoimmunity. Ann N Y Acad Sci 1317(1):84–91
Lemire JM, Archer DC, Beck L, Spiegelberg HL (1995) Immunosuppressive actions of 1, 25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 125:1704S-1708S
Boonstra A, Barrat FJ et al (2001) 1α, 25-Dihydroxyvitamin D3 has a direct effect on naive Cd4+ T cells to enhance the development of Th2 cells. J Immunol 167(9):4974–4980
Penna G, Amuchastegui S et al (2006) Treatment of experimental autoimmune prostatitis in nonobese diabetic mice by the vitamin D receptor agonist elocalcitol. J Immunol 177(12):8504–8511
Tang J, Zhou R et al (2009) Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th17 effector response. J Immunol 182(8):4624–4632
Joshi S, Pantalena L-C et al (2011) 1, 25-Dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17a. Mol Cell Biol 31(17):3653–3669
Cheng K, Ma C et al (2020) Vitamin D3 modulates yellow catfish (Pelteobagrus Fulvidraco) immune function in vivo and in vitro and this involves the vitamin D3/Vdr-type I interferon axis. Dev Comp Immunol 107:103644
Jiang J, Shi D et al (2015) Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus Carpio Var. Jian). Br J Nutr 114(10):1560–1568
Liu J, Shao R et al (2021) Vitamin D3 protects turbot (Scophthalmus Maximus L.) from bacterial infection. Fish Shellfish Immunol 118:25–33
Soto-Dávila M, Valderrama K et al (2020) Effects of vitamin D2 (Ergocalciferol) and D3 (Cholecalciferol) on Atlantic salmon (Salmo Salar) primary macrophage immune response to Aeromonas Salmonicida Subsp. Salmonicida infection Front Immunol 10:3011
Liao X, Lan Y et al (2022) Vitamin D enhances neutrophil generation and function in zebrafish (Danio Rerio). J Innate Immun 14(3):229–242
Song YJ, Zhang J et al (2023) Piscine vitamin D receptors Vdra/Vdrb in the absence of vitamin D are utilized by grass carp reovirus for promoting viral replication. Microbiol Spectrum 11(4):e01287-e1323
Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1, 25-Dihydroxyvitamin D3 receptors in human leukocytes. Science 221(4616):1181–1183
Baeke F, Korf H et al (2010) Human T lymphocytes are direct targets of 1, 25-dihydroxyvitamin D3 in the immune system. J Steroid Biochem Mol Biol 121(1–2):221–227
Hewison M, Freeman L et al (2003) Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol 170(11):5382–5390
Stoffels K, Overbergh L et al (2006) Immune regulation of 25-hydroxyvitamin-D3-1α-hydroxylase in human monocytes. J Bone Miner Res 21(1):37–47
Stoffels K, Overbergh L, Bouillon R, Mathieu C (2007) Immune regulation of 1α-hydroxylase in murine peritoneal macrophages: unravelling the Ifnγ pathway. J Steroid Biochem Mol Biol 103(3–5):567–571
Colotta F, Jansson B, Bonelli F (2017) Modulation of inflammatory and immune responses by vitamin D. J Autoimmun 85:78–97
Zhang Y, Leung DY et al (2012) Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting Mapk phosphatase-1. J Immunol 188(5):2127–2135
Wang Q, He Y et al (2014) Vitamin D inhibits Cox-2 expression and inflammatory response by targeting thioesterase superfamily member 4. J Biol Chem 289(17):11681–11694
Bogdanou D, Penna-Martinez M et al (2017) T-lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: a randomized controlled trial with sequential crossover. Diabetes Metab Res Rev 33(3):e2865
Chen Y, Liu W et al (2013) 1, 25-Dihydroxyvitamin D promotes negative feedback regulation of Tlr signaling via targeting microrna-155–Socs1 in macrophages. J Immunol 190(7):3687–3695
Liu PT, Stenger S et al (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311(5768):1770–1773
Chang J-M, Kuo M-C et al (2004) 1-Α, 25-Dihydroxyvitamin D3 regulates inducible nitric oxide synthase messenger Rna expression and nitric oxide release in macrophage-like raw 264.7 cells. J Lab Clin Med 143(1):14–22
Rockett KA, Brookes R et al (1998) 1, 25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun 66(11):5314–5321
Carlberg C (2019) Vitamin D signaling in the context of innate immunity: focus on human monocytes. Front Immunol 10:2211
Carlberg C (2017) Molecular endocrinology of vitamin D on the epigenome level. Mol Cell Endocrinol 453:14–21
Wang P, Huo X et al (2023) Vitamin D3 can effectively and rapidly clear largemouth bass ranavirus by immunoregulation. Fish Shellfish Immunol 143:109213
Gui B, Chen Q et al (2017) Effects of calcitriol (1, 25-dihydroxy-vitamin D3) on the inflammatory response induced by H9n2 influenza virus infection in human lung A549 epithelial cells and in mice. Virol J 14(1):1–11
Urashima M, Segawa T et al (2010) Randomized trial of vitamin D Supplementation to prevent seasonal influenza a in schoolchildren. Am J Clin Nutr 91(5):1255–1260
Osterholm MT, Kelley NS, Sommer A, Belongia EA (2012) Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12(1):36–44
Moan JE, Dahlback A, Ma L, Juzeniene A (2009) Influenza, solar radiation and vitamin D. Dermatoendocrinol 1(6):308–310
Sabetta JR, DePetrillo P et al (2010) Serum 25-hydroxyvitamin D and the incidence of acute viral respiratory tract infections in healthy adults. PLoS ONE 5(6):e11088
Bombardini T, Picano E (2020) Angiotensin-converting enzyme 2 as the molecular bridge between epidemiologic and clinical features of Covid-19. Can J Cardiol 36(5):784. E1-784. e2
Rehan VK, Torday JS et al (2002) 1α, 25-Dihydroxy-3-Epi-vitamin D3, a natural metabolite of 1α, 25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type Ii cells. Mol Genet Metab 76(1):46–56
Rondanelli M, Miccono A, Lamburghini S et al (2018) Self-care for common colds: the pivotal role of vitamin d, vitamin c, zinc, and echinacea in three main immune interactive clusters (Physical barriers, innate and adaptive immunity) Involved during an Episode of Common Colds-Practical Advice on Dosages and on the Time to Take These Nutrients/Botanicals in order to Prevent or Treat Common Colds. Evid Based Complement Alternat Med 2018:5813095. https://doi.org/10.1155/2018/5813095
Felsenstein S, Herbert JA, McNamara PS, Hedrich CM (2020) Covid-19: immunology and treatment options. Clin Immunol 215:108448
Grant WB, Lahore H et al (2020) Evidence that vitamin D supplementation could reduce risk of influenza and Covid-19 infections and deaths. Nutrients 12(4):988
Lelli D, Pérez Bazan L et al (2019) 25 (Oh) vitamin D and functional outcomes in older adults admitted to rehabilitation units: the Safari Study. Osteoporos Int 30:887–895
Liu X, Baylin A, Levy PD (2018) Vitamin D deficiency and insufficiency among Us adults: prevalence, predictors and clinical implications. Br J Nutr 119(8):928–936
Deplanque X, Wullens A, Norberciak L (2017) Prevalence and risk factors of vitamin D deficiency in healthy adults aged 18–65 years in Northern France. La Revue de Med Interne 38(6):368–373
Jolliffe DA, James WY et al (2018) Prevalence, determinants and clinical correlates of vitamin D deficiency in patients with chronic obstructive pulmonary disease in London, Uk. J Steroid Biochem Mol Biol 175:138–145
Kolls JK, Garry RF (2022) Role of the T cell vitamin D receptor in severe Covid-19. Nat Immunol 23(1):5–6
Alhammadin G, Jarrar Y, Madani A, Lee S-J (2023) Exploring the influence of Vdr genetic variants Taqi, Apai, and Foki on Covid-19 severity and long-Covid-19 symptoms. J Personal Med 13(12):1663
Bilezikian JP, Bikle D et al (2020) Mechanisms in endocrinology: vitamin D and Covid-19. Eur J Endocrinol 183(5):R133–R147
Silberstein M (2020) Correlation between premorbid Il-6 levels and Covid-19 mortality: potential role for vitamin D. Int Immunopharmacol 88:106995
Xu J, Yang J et al (2017) Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Report 16(5):7432–7438
Bouillon R, Carmeliet G et al (2008) Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 29(6):726–776
Christakos S, Dhawan P et al (2016) Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 96(1):365–408
Goyal P, Choi JJ et al (2020) Clinical characteristics of Covid-19 in New York City. N Engl J Med 382(24):2372–2374
Li YC, Qiao G et al (2004) Vitamin D: a negative endocrine regulator of the renin–angiotensin system and blood pressure. J Steroid Biochem Mol Biol 89:387–392
Pierce GN, Rupp H, Izumi T, Grynberg A (2013) Molecular and cellular effects of nutrition on disease processes. Vol. 26. Springer Science & Business Media
Babaali E, Rahmdel S et al (2020) Dietary intakes of zinc, copper, magnesium, calcium, phosphorus, and sodium by the general adult population aged 20–50 years in Shiraz, Iran: A Total Diet Study Approach. Nutrients 12(11):3370
Prasad AS (1979) Clinical, biochemical, and pharmacological role of zinc. Annu Rev Pharmacol Toxicol 19(1):393–426
Prasad AS (1983) Zinc deficiency in human subjects. Prog Clin Biol Res 129:1–33
Dhawan M, Emran TB, Choudhary OP (2022) Immunomodulatory effects of zinc and its impact on Covid-19 severity. Ann Med Surg 77:103638
Rahman MT, Idid SZ (2021) Can Zn be a critical element in Covid-19 treatment? Biol Trace Elem Res 199(2):550–558
Pvsn KK, Tomo S et al (2023) Comparative analysis of serum zinc, copper and magnesium level and their relations in association with severity and mortality in Sars-Cov-2 Patients. Biol Trace Elem Res 201(1):23–30
Shakoor H, Feehan J et al (2021) Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: could they help against Covid-19? Maturitas 143:1–9
Bin BH, Seo J, Kim ST (2018) Function, Structure, and Transport Aspects of ZIP and ZnT Zinc Transporters in Immune Cells. J Immunol Res 2018:9365747. https://doi.org/10.1155/2018/9365747
Mayer LS, Uciechowski P et al (2014) Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes. Metallomics 6(7):1288–1295
Haase H, Ober-Blöbaum JL et al (2008) Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes. J Immunol 181(9):6491–6502
Prasad AS (2008) Zinc in human health: effect of zinc on immune cells. Mol Med 14(5):353–357
Summersgill H, England H et al (2014) Zinc depletion regulates the processing and secretion of Il-1β. Cell Death Dis 5(1):e1040–e1040
Rodrigues TS, de Sá KSG, Ishimoto AY et al (2021) Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med 218(3):e20201707. https://doi.org/10.1084/jem.20201707
Amaral N, Rodrigues T et al (2023) Colchicine reduces the activation of Nlrp3 inflammasome in Covid-19 patients. Inflamm Res 72(5):895–899
Choi BY, Hong DK, Suh SW (2017) Znt3 gene deletion reduces colchicine-induced dentate granule cell degeneration. Int J Mol Sci 18(10):2189
Dawood MA, Alagawany M, Sewilam H (2021) The role of zinc microelement in aquaculture: a review. Biol Trace Elem Res 200:1–13
Paripatananont T, Lovell RT (1995) Responses of channel catfish fed organic and inorganic sources of zinc to Edwardsiella ictaluri challenge. J Aquat Anim Health 7(2):147–154
Mohseni M, Hamidoghli A, Bai SC (2021) Organic and inorganic dietary zinc in beluga sturgeon (Huso Huso): effects on growth, hematology, tissue concertation and oxidative capacity. Aquaculture 539:736672
Jintasataporn O, Ward T, Kattakdad S (2015) The efficacy of organic zinc amino acid complex (Availazn®) on growth performance and immunity of pangasius catfish (Pangasianodon Hypophthalmus). Aquac Indones 15:94–97
Lin S, Lin X et al (2013) Comparison of chelated zinc and zinc sulfate as zinc sources for growth and immune response of shrimp (Litopenaeus Vannamei). Aquaculture 406:79–84
Yang J, Wang T et al (2022) The assessment of dietary organic zinc on zinc homeostasis, antioxidant capacity, immune response, glycolysis and intestinal microbiota in white shrimp (Litopenaeus Vannamei Boone, 1931). Antioxidants 11(8):1492
Song Z-X, Jiang W-D et al (2017) Dietary zinc deficiency reduced growth performance, intestinal immune and physical barrier functions related to Nf-Κb, Tor, Nrf2, Jnk and Mlck signaling pathway of young grass carp (Ctenopharyngodon Idella). Fish Shellfish Immunol 66:497–523
Maares M, Haase H (2016) Zinc and immunity: an essential interrelation. Arch Biochem Biophys 611:58–65
Shin K, Fogg VC, Margolis B (2006) Tight junctions and cell polarity. Annu Rev Cell Dev Biol 22:207–235
Sturniolo GC, Fries W et al (2002) Effect of zinc supplementation on intestinal permeability in experimental colitis. J Lab Clin Med 139(5):311–315
Coperchini F, Chiovato L et al (2020) The cytokine storm in Covid-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 53:25–32
Skalny AV, Rink L et al (2020) Zinc and respiratory tract infections: perspectives for Covid-19. Int J Mol Med 46(1):17–26
Truong-Tran AQ, Carter J, Ruffin R, Zalewski PD (2001) New insights into the role of zinc in the respiratory epithelium. Immunol Cell Biol 79(2):170–177
Prasad AS (2007) Zinc: mechanisms of host defense. J Nutr 137(5):1345–1349
Suara RO, Crowe JE Jr (2004) Effect of zinc salts on respiratory syncytial virus replication. Antimicrob Agents Chemother 48(3):783–790
Te Velthuis AJ, van den Worm SH et al (2010) Zn2+ inhibits coronavirus and arterivirus Rna polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog 6(11):e1001176
Singh M, Das RR (2011) Zinc for the common cold. Cochrane Database Syst Rev (2):CD001364. https://doi.org/10.1002/14651858.CD001364.pub3
Fani M, Khodadad N et al (2020) Zinc sulfate in narrow range as an in vitro anti-Hsv-1 Assay. Biol Trace Elem Res 193:410–413
Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G (2019) The role of zinc in antiviral immunity. Adv Nutr 10(4):696–710
Berg K, Bolt G, Andersen H, Owen TC (2001) Zinc potentiates the antiviral action of human Ifn-Α tenfold. J Interferon Cytokine Res 21(7):471–474
Foster M, Samman S (2012) Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease. Nutrients 4(7):676–694
McCarty MF, DiNicolantonio JJ (2020) Nutraceuticals have potential for boosting the type 1 interferon response to rna viruses including influenza and coronavirus. Prog Cardiovasc Dis 63(3):383
McPherson SW, Keunen JE et al (2020) Investigate oral zinc as a prophylactic treatment for those at risk for Covid-19. Am J Ophthalmol 216:A5–A6
Speth R, Carrera E et al (2014) Concentration-dependent effects of zinc on angiotensin-converting enzyme-2 activity (10674). FASEB J 28:1067.4
Shittu MO, Afolami OI (2020) Improving the efficacy of chloroquine and hydroxychloroquine against Sars-Cov-2 may require zinc additives-a better synergy for future Covid-19 clinical trials. Infez Med 28(2):192–197
Krenn B, Gaudernak E et al (2009) Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections. J Virol 83(1):58–64
Kümel G, Schrader S et al (1990) The mechanism of the antiherpetic activity of zinc sulphate. J Gen Virol 71(12):2989–2997
Qiu M, Chen Y et al (2013) Zinc ionophores pyrithione inhibits herpes simplex virus replication through interfering with proteasome function and Nf-Κb activation. Antiviral Res 100(1):44–53
Liu CY, Kielian M (2012) Identification of a specific region in the E1 fusion protein involved in zinc inhibition of semliki forest virus fusion. J Virol 86(7):3588–3594
Ghaffari H, Tavakoli A et al (2019) Inhibition of H1n1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine. J Biomed Sci 26(1):1–10
Olechnowicz J, Tinkov A, Skalny A, Suliburska J (2018) Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci 68(1):19–31
Kim CH, Kim JH, Lee J, Ahn YS (2003) Zinc-induced Nf-Κb inhibition can be modulated by changes in the intracellular metallothionein level. Toxicol Appl Pharmacol 190(2):189–196
Costello LC, Guan Z, Franklin RB, Feng P (2004) Metallothionein can function as a chaperone for zinc uptake transport into prostate and liver mitochondria. J Inorg Biochem 98(4):664–666
Raymond AD, Gekonge B et al (2010) Increased metallothionein gene expression, zinc, and zinc-dependent resistance to apoptosis in circulating monocytes during Hiv viremia. J Leukoc Biol 88(3):589–596
Awad A, Zaglool AW, Ahmed SA, Khalil SR (2019) Transcriptomic profile change, immunological response and disease resistance of oreochromis niloticus fed with conventional and nano-zinc oxide dietary supplements. Fish Shellfish Immunol 93:336–343
Kishawy AT, Roushdy EM et al (2020) Comparing the effect of diet supplementation with different zinc sources and levels on growth performance, immune response and antioxidant activity of tilapia, Oreochromis niloticus. Aqua Nutr 26(6):1926–1942
Kumar N, Krishnani K et al (2017) Dietary zinc promotes immuno-biochemical plasticity and protects fish against multiple stresses. Fish Shellfish Immunol 62:184–194
Zihni C, Mills C, Matter K, Balda MS (2016) Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol 17(9):564–580
Bergelson JM (2009) Intercellular junctional proteins as receptors and barriers to virus infection and spread. Cell Host Microbe 5(6):517–521
Teoh K-T, Siu Y-L et al (2010) The sars coronavirus E protein interacts with Pals1 and alters tight junction formation and epithelial morphogenesis. Mol Biol Cell 21(22):3838–3852
Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1997) Biologia molecular da célula. In: Biologia molecular da célula. pp 1294–1294
Zhang Y-g, Wu S, Sun J (2013) Vitamin D, vitamin D receptor and tissue barriers. Tissue Barriers 1(1):e23118
Yin Z, Pintea V et al (2011) Vitamin D enhances corneal epithelial barrier function invest. Ophthalmol Vis Sci 52(10):7359–7364
Miyoshi Y, Tanabe S, Suzuki T (2016) Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression. Am J Physiol-Gastrointest Liver Physiol 311(1):G105–G116
Reyes J (2002) Lamas M, Martin D, Del Carmen Namorado M, Islas S, Luna J, Tauc M, and Gonzalez-Mariscal L. The renal segmental distribution of claudins changes with development. Kidney Int 62:476–487
Tarno H, Qi H et al (2011) Types of frass produced by the Ambrosia beetle platypus quercivorus during gallery construction, and host suitability of five tree species for the beetle. J For Res 16(1):68–75
Van Itallie CM, Anderson JM (2006) Claudins and epithelial paracellular transport. Annu Rev Physiol 68:403–429
Wang X, Valenzano MC et al (2013) Zinc supplementation modifies tight junctions and alters barrier function of Caco-2 human intestinal epithelial layers. Dig Dis Sci 58:77–87
Liu S-Z, Tan X-Y et al (2024) Interactive effect of dietary vitamin D3 and zinc (Zn) on growth performance, Zn metabolism, and intestinal health of yellow catfish Pelteobagrus fulvidraco. Aquaculture 578:740096
Campbell HK, Maiers JL, DeMali KA (2017) Interplay between tight junctions & adherens junctions. Exp Cell Res 358(1):39–44
Pálmer HG, González-Sancho JM et al (2001) Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of e-cadherin and the inhibition of Β-catenin signaling. J Cell Biol 154(2):369–388
Gumbiner BM (1996) Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell 84(3):345–357
Takeichi M (1995) Morphogenetic roles of classic cadherins. Curr Opin Cell Biol 7(5):619–627
Birchmeier W, Behrens J (1994) Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta (BBA)-Rev Cancer 1198(1):11–26
Christofori G, Semb H (1999) The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci 24(2):73–76
Perl A-K, Wilgenbus P et al (1998) A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392(6672):190–193
Finamore A, Massimi M, Conti Devirgiliis L, Mengheri E (2008) Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 Cells. J Nutr 138(9):1664–1670
Bao S, Knoell DL (2006) Zinc modulates cytokine-induced lung epithelial cell barrier permeability. Am J Physiol-Lung Cell Mol Physiol 291(6):L1132–L1141
Craig TA, Benson LM, Naylor S, Kumar R (2001) Modulation effects of zinc on the formation of vitamin D receptor and retinoid X receptor Α-DNA transcription complexes: analysis by microelectrospray mass spectrometry. Rapid Commun Mass Spectrom 15(12):1011–1016
Ndungo E, Randall A et al (2018) A novel Shigella proteome microarray discriminates targets of human antibody reactivity following oral vaccination and experimental challenge. Msphere 3(4):e00260-e318
Wessels I, Rolles B, Slusarenko AJ, Rink L (2022) Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of corona virus disease 19. Br J Nutr 127(2):214–232
Costagliola G, Spada E, Comberiati P, Peroni DG (2021) Could nutritional supplements act as therapeutic adjuvants in Covid-19? Ital J Pediatr 47(1):1–5
Chen K-Y, Lin C-K, Chen N-H (2023) Effects of vitamin D and zinc deficiency in acute and long Covid syndrome. J Trace Elem Med Biol 80:127278
Schmitt AK, Puppa M-A, Wessels I, Rink L (2022) Vitamin D3 and zinc synergistically induce regulatory T cells and suppress interferon-Γ production in mixed lymphocyte culture. J Nutr Biochem 102:108942
Tau G, Rothman P (1999) Biologic functions of the Ifn-Γ receptors. Allergy 54(12):1233
Rosenkranz E, Hilgers R-D et al (2017) Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects. Eur J Nutr 56:557–567
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The funding for this study was provided by the National Natural Science Foundation of China under grant number 32273147.
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M.R: Writing – original draft; investigation; data curation; software. K. C.: Investigation; resources. C. W: Writing – review and editing; project administration; supervision; funding acquisition. Y.G: Investigation; writing – original draft. Y. H.: Writing – review and editing; resources.
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Rizwan, M., Cheng, K., Gang, Y. et al. Immunomodulatory Effects of Vitamin D and Zinc on Viral Infection. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04139-y
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DOI: https://doi.org/10.1007/s12011-024-04139-y