{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:03:34Z","timestamp":1781870614062,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bio-Med-Chem Doctoral School, University of Lodz"},{"name":"Lodz Institutes of the Polish Academy of Sciences, Lodz, Poland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The Bacillus Calmette-Gu\u00e9rin (BCG) vaccine confers broad, non-specific immunity that may bolster defenses against respiratory viruses. While NOD2 (nucleotide-binding oligomerization domain-containing protein 2)-driven pathways are central to innate immune responses, the contribution of surface receptor modulation on monocytes to shaping these responses remains underexplored. We analyzed whole-blood cultures from BCG-vaccinated Polish children, stratified by serostatus to SARS-CoV-2 and RSV, and stimulated for 48 h with live BCG, purified viral antigens, or both. RT-qPCR quantified mRNA levels of NOD2 and key cytokines (IL-1\u03b2, IL-2, IL-4, IL-6, IL-8, IL-10, TNF), while flow cytometry assessed CD14, HLA-DR, CD11b, and CD206 expression. Co-stimulation with BCG + RSV elicited the strongest transcriptional response, notably a 2\u20134-fold upregulation of NOD2, IL-1\u03b2, and IL-6 versus RSV alone. In SARS-CoV-2(+) donors, RSV alone induced higher NOD2 expression than BCG or BCG + RSV, while IL-2 peaked following BCG + SARS-CoV-2. Across conditions, NOD2 positively correlated with IL-4 and IL-6 but negatively correlated with IL-1\u03b2 in SARS-CoV-2 cultures. Viral antigens increased CD14 and HLA-DR on monocytes, suggesting activation; CD206 rose only in dual-seropositive children. Our findings indicate that BCG stimulation affects pediatric antiviral immunity through NOD2-related cytokine production and induction of a CD14+HLA-DR+ phenotype, supporting its potential role in boosting innate defenses against respiratory pathogens.<\/jats:p>","DOI":"10.3390\/pathogens14070683","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:44:19Z","timestamp":1752241459000},"page":"683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["NOD2 (Nucleotide-Binding Oligomerization Domain-Containing Protein 2)-Mediated Modulation of the Immune Response Induced by BCG (Bacillus Calmette-Gu\u00e9rin) Bacilli"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5551-7707","authenticated-orcid":false,"given":"Magdalena","family":"Jurczak","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology, and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"},{"name":"The Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kaczmarek","sequence":"additional","affiliation":[{"name":"Regional Specialized Hospital of Tuberculosis, Lung Diseases and Rehabilitation in Lodz, Okolna 181, 91-520 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Kowalewska-Pietrzak","sequence":"additional","affiliation":[{"name":"Regional Specialized Hospital of Tuberculosis, Lung Diseases and Rehabilitation in Lodz, Okolna 181, 91-520 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Stelmach","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology, and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-4809","authenticated-orcid":false,"given":"Magdalena","family":"Druszczynska","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology, and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12967-023-03944-8","article-title":"BCG-Induced Trained Immunity: History, Mechanisms and Potential Applications","volume":"21","author":"Chen","year":"2023","journal-title":"J. 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