{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:26:27Z","timestamp":1787048787914,"version":"build-2736575974"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Background<\/jats:title>\n \n Bacterial lysates have been associated with improved host defense against respiratory infections; however, their mechanisms of action remain incompletely understood. Based on our previous\n in vitro<\/jats:italic>\n work showing that Pulmonarom\n \u00ae<\/jats:sup>\n activates human monocyte-derived dendritic cells (moDCs) and induces TLR- and cytokine-related responses consistent with innate immune activation, we evaluated its immunomodulatory effect during influenza A virus infection using two\n in vitro<\/jats:italic>\n conditions: pre-exposure and post-infection treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n Human monocytes obtained from buffy coats were differentiated into moDCs. Lyophilized Pulmonarom\n \u00ae<\/jats:sup>\n was quantified as total protein and evaluated at 0.01, 0.1, or 0.5 \u00b5g\/mL in 24-well cultures containing 1 \u00d7 10\n 6<\/jats:sup>\n moDCs in 1 mL medium per well. In the pre-exposure condition, moDCs were incubated with Pulmonarom\n \u00ae<\/jats:sup>\n for 1\u00a0h before infection with influenza A\/H1N1 or A\/H3N2 virus. In the post-infection treatment condition, Pulmonarom\n \u00ae<\/jats:sup>\n was added after the 1-h infection period. TLRs and cytokine expression were evaluated by flow cytometry. Changes in hemagglutinating activity were evaluated by hemagglutination inhibition assay and virus infectivity was evaluated with a MDCK plaque cell assay.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Under both pre-exposure and post-infection treatment conditions, Pulmonarom\n \u00ae<\/jats:sup>\n enhanced MHC class II expression and improved cell viability following infection with either A\/H1N1 or A\/H3N2 virus, consistent with moDC activation. In hemagglutination inhibition assays, Pulmonarom\n \u00ae<\/jats:sup>\n was associated with reduced hemagglutinating activity in culture supernatants. Similarly, plaque infectivity assays demonstrated that Pulmonarom\n \u00ae<\/jats:sup>\n , administered either before or after infection, decreased the number of lysed cells within plaques, with a more pronounced effect observed under post-infection treatment. These immunomodulatory changes were accompanied by increased cytokine secretion and the induction of type I interferon-related responses.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Pulmonarom\n \u00ae<\/jats:sup>\n modulated human moDC responses during\n in vitro<\/jats:italic>\n infection with influenza A\/H1N1 and A\/H3N2 virus. These findings extend our previous observations on Pulmonarom\n \u00ae<\/jats:sup>\n -induced innate immune activation in human dendritic cells and support further analysis of this bacterial lysate as a host-directed immunomodulatory strategy. Future studies should be evaluated to determine infectious viral titers, TLRs dependency, dendritic-cell maturation markers, and downstream T-cell responses; using plaque assay with sensible cells, receptor-blocking approaches, expanded maturation and characterization panels, and functional co-culture assays.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1891757","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:41:33Z","timestamp":1787046093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonarom\u00ae promotes TLR-related and interferon-related antiviral responses during influenza A (H1N1 and H3N2) infection in human monocyte-derived dendritic cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Sandra Georgina","family":"Solano-G\u00e1lvez","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n Universidad Nacional Aut\u00f3noma de 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