{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:53:02Z","timestamp":1792194782960,"version":"4.4.0"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes \u03b2-defensin 2\/defensin-\u03b24 (HBD2\/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2\/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2\/DEFB4 contribute to antiviral immunity.<\/jats:p>","DOI":"10.3390\/nu14020284","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T20:33:04Z","timestamp":1641933184000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":131,"title":["Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity"],"prefix":"10.3390","volume":"14","author":[{"given":"John H.","family":"White","sequence":"first","affiliation":[{"name":"Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0021-9258(18)85783-0","article-title":"Studies on experimental rickets: XXI. an experimental demonstration of the existence of a vitamin which promotes calcium deposition","volume":"53","author":"McCollum","year":"1922","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/jn\/134.6.1299","article-title":"The Discovery of Vitamin D: The Contribution of Adolf Windaus","volume":"134","author":"Wolf","year":"2004","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1126\/science.6251551","article-title":"Photosynthesis of Previtamin D3 in Human Skin and the Physiologic Consequences","volume":"210","author":"Holick","year":"1980","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15650","DOI":"10.1073\/pnas.1315006110","article-title":"CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo","volume":"110","author":"Zhu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7711","DOI":"10.1073\/pnas.0402490101","article-title":"Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase","volume":"101","author":"Cheng","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions","volume":"40","author":"Bouillon","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_7","first-page":"888","article-title":"Extrarenal Expression of 25-Hydroxyvitamin D3-1\u03b1-Hydroxylase","volume":"86","author":"Zehnder","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1046\/j.1365-2249.2000.01204.x","article-title":"Identification and immune regulation of 25-hydroxyvitamin D-1-\u03b1-hydroxylase in murine macrophages","volume":"120","author":"Overbergh","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1126\/science.1123933","article-title":"Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response","volume":"311","author":"Liu","year":"2006","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22593","DOI":"10.1073\/pnas.1011624108","article-title":"T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism","volume":"107","author":"Edfeldt","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11154-011-9195-z","article-title":"Vitamin D metabolism and signaling in the immune system","volume":"13","author":"White","year":"2012","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Martens, P.-J., Gysemans, C., Verstuyf, A., and Mathieu, C. (2020). Vitamin D\u2019s Effect on Immune Function. Nutrients, 12.","DOI":"10.3390\/nu12051248"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e10405","DOI":"10.1002\/jbm4.10405","article-title":"Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory","volume":"5","author":"Bishop","year":"2021","journal-title":"JBMR Plus"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern Recognition Receptors and Inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.4049\/jimmunol.150.8.3487","article-title":"Functional antagonism between vitamin D3 and retinoic acid in the regulation of CD14 and CD23 expression during monocytic differentiation of U-937 cells","volume":"150","author":"Oberg","year":"1993","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1172\/JCI30142","article-title":"Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism","volume":"117","author":"Schauber","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1074\/jbc.C109.071225","article-title":"Direct and Indirect Induction by 1,25-Dihydroxyvitamin D3 of the NOD2\/CARD15-Defensin \u03b22 Innate Immune Pathway Defective in Crohn Disease","volume":"285","author":"Wang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Verway, M., Bouttier, M., Wang, T.-T., Carrier, M., Calderon, M., An, B.-S., Devemy, E., McIntosh, F., Divangahi, M., and Behr, M.A. (2013). Vitamin D Induces Interleukin-1\u03b2 Expression: Paracrine Macrophage Epithelial Signaling Controls M-tuberculosis Infection. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003407"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.4049\/jimmunol.173.5.2909","article-title":"Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression","volume":"173","author":"Wang","year":"2004","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.3390\/ph6121543","article-title":"Antimicrobial Peptides","volume":"6","author":"Bahar","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R14","DOI":"10.1016\/j.cub.2015.11.017","article-title":"Antimicrobial peptides","volume":"26","author":"Zhang","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/415389a","article-title":"Antimicrobial peptides of multicellular organisms","volume":"415","author":"Zasloff","year":"2002","journal-title":"Nature"},{"key":"ref_23","first-page":"8","article-title":"Sunlight in Tuberculosis","volume":"1","author":"Masten","year":"1935","journal-title":"Chest"},{"key":"ref_24","first-page":"112","article-title":"The history of cod liver oil as a remedy","volume":"26","author":"Guy","year":"1923","journal-title":"Am. J. Dis. Child."},{"key":"ref_25","first-page":"106","article-title":"Cod and the Consumptive: A Brief History of Cod-Liver Oil in the Treatment of Pulmonary Tuberculosis","volume":"46","author":"Grad","year":"2004","journal-title":"Pharm. Hist."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.jsbmb.2006.12.052","article-title":"Vitamin D in the treatment of pulmonary tuberculosis","volume":"103","author":"Martineau","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/sj.jid.5701043","article-title":"In vitro and In vivo Wound Healing-Promoting Activities of Human Cathelicidin LL-37","volume":"128","author":"Carretero","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1046\/j.1523-1747.2003.12069.x","article-title":"The Cathelicidin Anti-Microbial Peptide LL-37 is Involved in Re-Epithelialization of Human Skin Wounds and is Lacking in Chronic Ulcer Epithelium","volume":"120","author":"Heilborn","year":"2003","journal-title":"J. Investig. Derm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/jid.2008.35","article-title":"Vitamin D Regulation of Cathelicidin in the Skin: Toward a Renaissance of Vitamin D in Dermatology?","volume":"128","author":"Segaert","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1096\/fj.04-3284com","article-title":"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","volume":"19","author":"Gombart","year":"2005","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gombart, A., Saito, T., and Koeffler, H.P. (2009). Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-321"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jsbmb.2015.09.016","article-title":"Species-specific regulation of innate immunity by vitamin D signaling","volume":"164","author":"Dimitrov","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e000211","DOI":"10.1136\/bmjresp-2017-000211","article-title":"Effect of vitamin D3 on the antimicrobial activity of human airway surface liquid: Preliminary results of a randomised placebo-controlled double-blind trial","volume":"4","author":"Cano","year":"2017","journal-title":"BMJ Open Respir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"g2035","DOI":"10.1136\/bmj.g2035","article-title":"Vitamin D and multiple health outcomes: Umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials","volume":"348","author":"Theodoratou","year":"2014","journal-title":"BMJ"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12937-018-0318-1","article-title":"Vitamin D status and dental caries in healthy Swedish children","volume":"17","author":"Gyll","year":"2018","journal-title":"Nutr. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6147","DOI":"10.1007\/s00784-021-03914-8","article-title":"Association of parental-reported vitamin D supplementation with dental caries of 3-year-old children in Poland: A cross-sectional study","volume":"25","author":"Kaczmarek","year":"2021","journal-title":"Clin. Oral Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1753-4887.2012.00544.x","article-title":"Vitamin D and dental caries in controlled clinical trials: Systematic review and meta-analysis","volume":"71","author":"Hujoel","year":"2013","journal-title":"Nutr. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1111\/iej.13130","article-title":"Heparin-LL37 complexes are less cytotoxic for human dental pulp cells and have undiminished antimicrobial and LPS-neutralizing abilities","volume":"52","author":"Yoshida","year":"2019","journal-title":"Int. Endod. J."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hertting, O., Holm, \u00c5., L\u00fcthje, P., Brauner, H., Dyrdak, R., Jonasson, A.F., Wiklund, P., Chromek, M., and Brauner, A. (2010). Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015580"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/apa.14499","article-title":"Association between vitamin D, antimicrobial peptides and urinary tract infection in infants and young children","volume":"108","author":"Georgieva","year":"2019","journal-title":"Acta Paediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"325","DOI":"10.4274\/jcrpe.2563","article-title":"The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection","volume":"8","author":"Altun","year":"2016","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1159\/000370046","article-title":"The association between vitamin D levels and urinary tract infection in children","volume":"83","author":"Tekin","year":"2015","journal-title":"Horm. Res. Paediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e1121","DOI":"10.1016\/j.ijid.2013.06.007","article-title":"The association between serum levels of vitamin D and recurrent urinary tract infections in premenopausal women","volume":"17","author":"Nseir","year":"2013","journal-title":"Int. J. Infect. Dis."},{"key":"ref_44","first-page":"134","article-title":"Vitamin D and urinary tract infection: A systematic review and meta-analysis","volume":"49","author":"Deng","year":"2019","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5556354","DOI":"10.1155\/2021\/5556354","article-title":"NAFLD and Infection, a Nuanced Relationship","volume":"2021","author":"Adenote","year":"2021","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1002\/hep.26390","article-title":"Vitamin D and nonalcoholic fatty liver disease (NAFLD): Is it more than just an association?","volume":"58","author":"Kwok","year":"2013","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41574-019-0156-z","article-title":"Gut microbial metabolites in obesity, NAFLD and T2DM","volume":"15","author":"Canfora","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"G542","DOI":"10.1152\/ajpgi.00286.2019","article-title":"Vitamin D signaling maintains intestinal innate immunity and gut microbiota: Potential intervention for metabolic syndrome and NAFLD","volume":"318","author":"Zeng","year":"2020","journal-title":"Am. J. Physiol.-Gastroint. Liver Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/ijo.2016.90","article-title":"Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor","volume":"40","author":"Mattai","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jsbmb.2016.12.015","article-title":"Vitamin D deficiency and the pathogenesis of Crohn\u2019s disease","volume":"175","author":"White","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12662","DOI":"10.1097\/MD.0000000000012662","article-title":"Efficacy of vitamin D in treatment of inflammatory bowel disease: A meta-analysis","volume":"97","author":"Li","year":"2018","journal-title":"Medicine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1111\/apt.15506","article-title":"Systematic review with meta-analysis: Association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease","volume":"50","author":"Gubatan","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1007\/s10620-015-3620-1","article-title":"Vitamin D Status Is Associated with Intestinal Inflammation as Measured by Fecal Calprotectin in Crohn\u2019s Disease in Clinical Remission","volume":"60","author":"Raftery","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tran, D.H.-N., Wang, J., Ha, C., Ho, W., Mattai, S.A., Oikonomopoulos, A., Weiss, G., Lacey, P., Cheng, M., and Shieh, C. (2017). Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn\u2019s disease, and clinical prognosis in inflammatory bowel disease. BMC Gastroenterol., 17.","DOI":"10.1186\/s12876-017-0619-4"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn\u2019s disease","volume":"411","author":"Hugot","year":"2001","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nri2340","article-title":"The genetics and immunopathogenesis of inflammatory bowel disease","volume":"8","author":"Cho","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1086\/505915","article-title":"A Chromosome 8 Gene-Cluster Polymorphism with Low Human Beta-Defensin 2 Gene Copy Number Predisposes to Crohn Disease of the Colon","volume":"79","author":"Fellermann","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1002\/ibd.21537","article-title":"Antimicrobial peptide response to blood translocation of bacterial DNA in Crohn\u2019s disease is affected by NOD2\/CARD15 genotype","volume":"17","author":"Holler","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lee, C. (2020). Controversial effects of vitamin D and related genes on viral infections, pathogenesis, and treatment outcomes. Nutrients, 12.","DOI":"10.3390\/nu12040962"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"i6583","DOI":"10.1136\/bmj.i6583","article-title":"Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data","volume":"356","author":"Martineau","year":"2017","journal-title":"BMJ"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S2213-8587(21)00051-6","article-title":"Vitamin D supplementation to prevent acute respiratory infections: A systematic review and meta-analysis of aggregate data from randomised controlled trials","volume":"9","author":"Jolliffe","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1146\/annurev-immunol-042617-053309","article-title":"RIG-I and Other RNA Sensors in Antiviral Immunity","volume":"36","author":"Chow","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.virusres.2015.11.024","article-title":"Antiviral innate immunity through the lens of systems biology","volume":"218","author":"Tripathi","year":"2016","journal-title":"Virus Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7090","DOI":"10.4049\/jimmunol.181.10.7090","article-title":"Respiratory epithelial cells convert inactive vitamin D to its active form: Potential effects on host defense","volume":"181","author":"Hansdottir","year":"2008","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.antiviral.2016.11.004","article-title":"Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro","volume":"137","author":"Telcian","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"27614","DOI":"10.1074\/jbc.M114.582973","article-title":"LL-37 peptide enhancement of signal transduction by Toll-like receptor 3 is regulated by pH: Identification of a peptide antagonist of LL-37","volume":"289","author":"Singh","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature06116","article-title":"Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide","volume":"449","author":"Lande","year":"2007","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1084\/jem.20090480","article-title":"Self-RNA\u2013antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8","volume":"206","author":"Ganguly","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.3389\/fimmu.2020.01137","article-title":"Cathelicidins Modulate TLR-Activation and Inflammation","volume":"11","author":"Scheenstra","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/jid.2011.259","article-title":"Cathelicidin Antimicrobial Peptide LL-37 in Psoriasis Enables Keratinocyte Reactivity against TLR9 Ligands","volume":"132","author":"Morizane","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"620806","DOI":"10.3389\/fmolb.2021.620806","article-title":"Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2","volume":"8","author":"Ghosh","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_73","first-page":"2","article-title":"A narrative review of influenza: A seasonal and pandemic disease","volume":"42","author":"Moghadami","year":"2017","journal-title":"Iran. J. Med. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1099\/vir.0.045013-0","article-title":"The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins","volume":"94","author":"Tripathi","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Meng, J., Stobart, C.C., Hotard, A.L., and Moore, M.L. (2014). An overview of respiratory syncytial virus. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004016"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Currie, S.M., Findlay, E.G., McHugh, B.J., Mackellar, A., Man, T., Macmillan, D., Wang, H., Fitch, P.M., Schwarze, J., and Davidson, D.J. (2013). The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073659"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.4049\/jimmunol.1502478","article-title":"Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans","volume":"196","author":"Currie","year":"2016","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Brockman-Schneider, R.A., Pickles, R.J., and Gern, J.E. (2014). Effects of vitamin D on airway epithelial cell morphology and rhinovirus replication. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086755"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1183\/13993003.00665-2015","article-title":"Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37","volume":"47","author":"Muster","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_80","unstructured":"Ismailova, A., and White, J.H. (2021). Vitamin D, infections and immunity. Rev. Endocr. Metab. Disord., 1\u201313."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Zhang, L., Ghosh, S.K., Basavarajappa, S.C., Muller-Greven, J., Penfield, J., Brewer, A., Ramakrishnan, P., Buck, M., and Weinberg, A. (2021). hBD-2 Binds SARS-CoV-2 RBD and Blocks Viral Entry: Strategy to Combat COVID-19. Sneak Peek.","DOI":"10.2139\/ssrn.3789259"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lokhande, K.B., Banerjee, T., Swamy, K.V., Ghosh, P., and Deshpande, M. (2021). An in silico scientific basis for LL-37 as a therapeutic for Covid-19. Proteins Struct. Funct. Bioinform., 1\u201315.","DOI":"10.26434\/chemrxiv.12928202"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhang, L., Ghosh, S.K., Basavarajappa, S.C., Muller-Greven, J., Penfield, J., Brewer, A., Ramakrishnan, P., Buck, M., and Weinberg, A. (2021). Molecular dynamics simulations and functional studies reveal that hBD-2 binds SARS-CoV-2 spike RBD and blocks viral entry into ACE2 expressing cells. bioRxiv.","DOI":"10.1101\/2021.01.07.425621"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1021\/acsinfecdis.1c00096","article-title":"Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone","volume":"7","author":"Wang","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhao, Y., Jiang, X., Zhao, Y., Yang, L., Chen, L., Dong, M., Luan, Z., Yan, C., and Jiao, J. (2020). Preliminary evaluation of the safety and efficacy of oral human antimicrobial peptide LL-37 in the treatment of patients of COVID-19, a small-scale, single-arm, exploratory safety study. medRxiv.","DOI":"10.1101\/2020.05.11.20064584"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/2\/284\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:27:07Z","timestamp":1760362027000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/2\/284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,11]]},"references-count":85,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["nu14020284"],"URL":"https:\/\/doi.org\/10.3390\/nu14020284","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.741550196.793591642","asserted-by":"object"}]},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,11]]}}}