{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:04:15Z","timestamp":1790251455556,"version":"4.1.0"},"reference-count":27,"publisher":"BioExcel","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["DIC"],"abstract":"<jats:p>Background: Immunostimulants were established many years ago to improve the capacity of the immune system to react to exogenous noxae. Immunostimulants can be synthesized in the lab or extracted from bacterial cultures. For example, bacterial lysates have been shown to have a significant effect on the number of infectious episodes, duration of fever and use of antibiotics in patients affected by recurrent respiratory tract infections. The capacity of bacterial lysates to induce the maturation of human monocyte-derived dendritic cells (DCs) has been indicated as the first and fundamental effect focused on the activation of an efficient immune response. Synthetic drugs, used in clinics in the prophylaxis of recurrent respiratory tract infections, have also been described to induce the maturation of DCs. Pidotimod, one of the most representative immunostimulant drugs, has been proposed to induce DC maturation. However, an optimal maturation of DCs is needed to achieve an efficient immune response.\n\nMethods: We evaluated the capacity of pidotimod in inducing the maturation of DCs using a prototypic bacterial lysate, Lantigen B, as a control. This maturation was detected using a monocyte-derived DC maturation assay, measured as an increase in the expression of the CD83 and CD86 and the secretion of IL-1\u03b2, IL-12 and IL-23, three pivotal cytokines for the activation of an efficient immune response.\n\nResults: In the current experimental conditions, 10, 1 and 0.1 \u03bcg of pidotimod had no effects on DCs, whilst Lantigen B was able to induce complete maturation of DCs in vitro. Additionally, the same doses of pidotimod used in conjunction with Lantigen B also had no further effect on DC maturation induced by the bacterial lysate.\n\nConclusion: These findings seem to support the concept that bacterial lysates are more effective than other synthetic immunostimulants in inducing an efficient immune response able to affect the incidence and severity of airway infections.\n\nDownload the Plain Language Summary of this article: https:\/\/www.drugsincontext.com\/plain-language-summaries\/plain-language-summary-immunostimulant-induced-maturation-of-monocytederived-dendritic-cells-in-respiratory-infection-prophylaxis<\/jats:p>","DOI":"10.7573\/dic.2025-12-1","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:35:47Z","timestamp":1777278947000},"page":"1","source":"Crossref","is-referenced-by-count":0,"title":["Immunostimulant-induced maturation of monocyte derived dendritic cells in respiratory infection prophylaxis"],"prefix":"10.7573","volume":"15","author":[{"given":"Kanta","family":"Basharat","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0107c5v14","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Genoa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Ferraris","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0107c5v14","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Genoa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"Braido","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0107c5v14","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Genoa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Melioli","sequence":"additional","affiliation":[{"name":"Alliance Medical Diagnostic Ltd, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10047","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"1.\tTorres A, Cilloniz C, Aldea M, et al. Adult vaccinations against respiratory infections. Expert Rev Anti Infect Ther. 2025;23(2\u20134):135\u2013147. https:\/\/doi.org\/10.1080\/14787210.2025.2457464","DOI":"10.1080\/14787210.2025.2457464"},{"key":"ref1","doi-asserted-by":"crossref","unstructured":"2.\tMelioli G, Passalacqua G, Baena-Cagnani CE, Canonica GW. Allergens and bacteria interaction in the induction of basophil activation: is this the lost ring between allergy and infections in pediatric patients? Curr Opin Allergy Clin Immunol. 2012;12(2):164\u2013170. https:\/\/doi.org\/10.1097\/ACI.0b013e328350fd91","DOI":"10.1097\/ACI.0b013e328350fd91"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"3.\tPoulos LM, Ampon RD, Marks GB, Reddel HK. Inappropriate prescribing of inhaled corticosteroids: are they being prescribed for respiratory tract infections? A retrospective cohort study. Prim Care Respir J 2013;22(2):201\u2013208. https:\/\/doi.org\/10.4104\/pcrj.2013.00036","DOI":"10.4104\/pcrj.2013.00036"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"4.\tBassetti M, Andreoni M, Santus P, Scaglione F. NSAIDs for early management of acute respiratory infections. Curr Opin Infect Dis. 2024;37(4):304\u2013311. https:\/\/doi.org\/10.1097\/QCO.0000000000001024","DOI":"10.1097\/QCO.0000000000001024"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"5.\tD\u2019Amico R, Pifferi S, Torri V, Brazzi L, Parmelli E, Liberati A. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev. 2009;2009(4):CD000022. https:\/\/doi. org\/10.1002\/14651858.CD000022.pub3","DOI":"10.1002\/14651858.CD000022.pub3"},{"key":"ref5","unstructured":"6.\tBraido F, Melioli G, Nicolini G, Canonica GW. Prevention of recurrent respiratory tract infections: a literature review of the activity of the bacterial lysate Lantigen B. Eur Rev Med Pharmacol Sci. 2023;27(16):7756\u20137767. https:\/\/doi. org\/10.26355\/eurrev_202308_33430"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"7.\tBraido F, Melioli G, Nicolini G, et al. Sublingually administered bacterial lysates: rationale, mechanisms of action and clinical outcomes. Drugs Context. 2024;13:2024-1-5. https:\/\/doi.org\/10.7573\/dic.2024-1-5","DOI":"10.7573\/dic.2024-1-5"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"8.\tPuggioni F, Alves-Correia M, Mohamed MF, et al. Immunostimulants in respiratory diseases: focus on Pidotimod. Multidiscip Respir Med. 2019;14:31. https:\/\/doi.org\/10.1186\/s40248-019-0195-2","DOI":"10.4081\/mrm.2019.50"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"9.\tBuend\u00eda JA, Guerrero Pati\u00f1o D, Lindarte EF. Podotimod in pediatric recurrent respiratory tract infections: a cost-utility analysis. BMC Pulm Med. 2022;22(1):244. https:\/\/doi.org\/10.1186\/s12890-022-02029-4","DOI":"10.1186\/s12890-022-02029-4"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"10.\tMeng Y, Wang Q, Zhang Z, et al. Synergistic effect of methionine encephalin (MENK) combined with pidotimod(PTD) on the maturation of murine dendritic cells (DCs). Hum Vaccines Immunother. 2013;9(4):773\u2013783. https:\/\/doi. org\/10.4161\/hv.23137","DOI":"10.4161\/hv.23137"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"11.\tHu S, Fu X, Fu A, Du W, Ji J, Li W. The regulatory peptide pidotimod facilitates M2 macrophage polarization and its function. Amino Acids. 2014;46(5):1177\u20131185. https:\/\/doi.org\/10.1007\/s00726-014-1676-4","DOI":"10.1007\/s00726-014-1676-4"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"12.\tHu X, Zhang W, Wang L, et al. The detailed analysis of the changes of murine dendritic cells (DCs) induced by thymic peptide: pidotimod (PTD). Hum Vaccines Immunother. 2012;8(9):1250\u20131258. https:\/\/doi.org\/10.4161\/hv.20579","DOI":"10.4161\/hv.20579"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"13.\tGiagulli C, Noerder M, Avolio M, et al. Pidotimod promotes functional maturation of dendritic cells and displays adjuvant properties at the nasal mucosa level. Int Immunopharmacol. 2009;9(12):1366\u20131373. https:\/\/doi. org\/10.1016\/j.intimp.2009.08.010","DOI":"10.1016\/j.intimp.2009.08.010"},{"key":"ref13","unstructured":"14.\tFogli M, Caccuri F, Iaria ML, et al. The immunomodulatory molecule pidotimod induces the expression of the NOD-like receptor NLRP12 and attenuates TLR-induced inflammation. J Biol Regul Homeost Agents. 2014;28(4):753\u2013766."},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"15.\tCarta S, Silvestri M, Rossi GA. Modulation of airway epithelial cell functions by pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. Ital J Pediatr. 2013;39:29. https:\/\/doi.org\/10.1186\/1824-7288-39-29","DOI":"10.1186\/1824-7288-39-29"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"16.\tSidoti Migliore G, Pezzino G, Cavaliere R, De Pasquale C, Ferlazzo G. On immunostimulants and dendritic cell activation. Immunol Lett. 2021;232:45\u201347. https:\/\/doi.org\/10.1016\/j.imlet.2021.02.004","DOI":"10.1016\/j.imlet.2021.02.004"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"17.\tZhou LJ, Tedder TF. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J Immunol. 1995;154(8):3821\u20133835. https:\/\/doi.org\/10.4049\/jimmunol.154.8.3821","DOI":"10.4049\/jimmunol.154.8.3821"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"18.\tLanier LL, O\u2019Fallon S, Somoza C, et al. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J Immunol. 1995;154(1):97\u2013105. https:\/\/doi.org\/10.4049\/ jimmunol.154.1.97","DOI":"10.4049\/jimmunol.154.1.97"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"19.\tCavalli G, Colafrancesco S, Emmi G, et al. Interleukin 1\u03b1: a comprehensive review on the role of IL-1\u03b1 in the pathogenesis and treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 2021;20(3):102763. https:\/\/doi.org\/10.1016\/j.autrev.2021.102763","DOI":"10.1016\/j.autrev.2021.102763"},{"key":"ref19","unstructured":"20.\tUllrich KAM, Schulze LL, Paap EM, et al. Immunology of IL-12: an update on functional activities and implications for disease. EXCLI J. 2020;19:1563\u20131589. https:\/\/doi.org\/10.17179\/excli2020-3104"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"21.\tKrueger JG, Eyerich K, Kuchroo VK, et al. IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol. 2024;15:1331217. https:\/\/doi.org\/10.3389\/fimmu.2024.1331217","DOI":"10.3389\/fimmu.2024.1331217"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"22.\tMorandi B, Agazzi A, D\u2019Agostino A, et al. A mixture of bacterial mechanical lysates is more efficient than single strain lysate and of bacterial-derived soluble products for the induction of an activating phenotype in human dendritic cells. Immunol Lett. 2011;138(1):86\u201391. https:\/\/doi.org\/10.1016\/j.imlet.2011.03.006","DOI":"10.1016\/j.imlet.2011.03.006"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"23.\tFerlazzo G, Semino C, Melioli G. HLA class I molecule expression is upregulated during maturation of dendritic cells, protecting them from natural killer cell-mediated lysis. Immunol Lett. 2001;76(1):37\u201341. https:\/\/doi.org\/10.1016\/S0165- 2478(00)00323-0","DOI":"10.1016\/S0165-2478(00)00323-0"},{"key":"ref23","unstructured":"24.\tRinaldi G. Lantigen B e le infezioni respiratorie. Novit\u00e0 immunologiche e profilassi. Farmaci. 2007;31:5\u201321."},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"25.\tSteinman RM, Turley S, Mellman I, Inaba K. The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med. 2000;191(3):411\u2013416. https:\/\/doi.org\/10.1084\/jem.191.3.411","DOI":"10.1084\/jem.191.3.411"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"26.\tSteinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21(1):685\u2013711. https:\/\/doi.org\/10.1146\/annurev.immunol.21.120601.141040","DOI":"10.1146\/annurev.immunol.21.120601.141040"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"27.\tMoretta A. Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol. 2002;2(12):957\u2013 965. https:\/\/doi.org\/10.1038\/nri956","DOI":"10.1038\/nri956"}],"container-title":["Drugs in Context"],"original-title":[],"link":[{"URL":"https:\/\/www.drugsincontext.com\/wp-content\/uploads\/2026\/04\/dic.2025-12-1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:14:47Z","timestamp":1790248487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.drugsincontext.com\/immunostimulant-induced-maturation-of-monocytederived-dendritic-cells-in-respiratory-infection-prophylaxis"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":27,"URL":"https:\/\/doi.org\/10.7573\/dic.2025-12-1","relation":{},"ISSN":["1740-4398"],"issn-type":[{"value":"1740-4398","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"article-number":"dic.2025-12-1"}}