PMID- 30830942 OWN - NLM STAT- MEDLINE DCOM- 20191202 LR - 20200309 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 3 DP - 2019 TI - Hydroalcoholic extract from Origanum vulgare induces a combined anti-mycobacterial and anti-inflammatory response in innate immune cells. PG - e0213150 LID - 10.1371/journal.pone.0213150 [doi] LID - e0213150 AB - In nature, many plants or their extracted compounds have been found to possess anti-inflammatory features and therapeutic properties against infectious as well as non-infectious diseases, including cancer. In this study, we analysed the immunomodulatory effects on innate immune cells of hydroalcoholic extract from Origanum vulgare L. ssp. hirtum (HyE-Ov), a plant traditionally known for its anti-oxidative properties. The effects of HyE-Ov were tested on human monocyte derived dendritic cells (DC), type-1 (M1) and type-2 macrophages (M2) infected with M. bovis Bacille Calmette-Guerin (BCG), used as a model of persistent intracellular bacterium. DC, M1 and M2 treated with HyE-Ov significantly enhanced their mycobactericidal activity, which was associated with phagosomal acidification in M1 and M2 and increase of phagosomal, but not mitochondrial ROS production in M1, M2, and DC. Treatment of BCG-infected DC with HyE-Ov significantly reduced TNF-alpha and IL-12 production and increased TGF-beta synthesis. Finally, experiments were repeated using eight different HPLC fractions of HyE-Ov. Results showed that the capability to activate anti-microbial and anti-inflammatory response is shared by different fractions, suggesting that diverse bioactive molecules are present within the hydroalcoholic extract. Altogether, these results show that HyE-Ov promotes anti-mycobacterial innate immunity and limits inflammatory response in vitro and suggest that this plant extract may be exploitable as phytocomplex or nutraceutical for novel host-directed therapeutic approaches. FAU - De Santis, Federica AU - De Santis F AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. FAU - Poerio, Noemi AU - Poerio N AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. FAU - Gismondi, Angelo AU - Gismondi A AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. FAU - Nanni, Valentina AU - Nanni V AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. FAU - Di Marco, Gabriele AU - Di Marco G AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. FAU - Nisini, Roberto AU - Nisini R AD - Department of infectious diseases, Istituto Superiore di Sanita, Rome, Italy. FAU - Thaller, Maria Cristina AU - Thaller MC AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. FAU - Canini, Antonella AU - Canini A AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. FAU - Fraziano, Maurizio AU - Fraziano M AUID- ORCID: 0000-0002-5643-0769 AD - Department of Biology, University of Rome "Tor Vergata", Rome, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190304 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Alcohols) RN - 0 (Anti-Infective Agents) RN - 0 (Anti-Inflammatory Agents) RN - 0 (IL2 protein, human) RN - 0 (Interleukin-2) RN - 0 (Plant Extracts) RN - 0 (TNF protein, human) RN - 0 (Transforming Growth Factor beta) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Alcohols/chemistry/*pharmacology MH - Anti-Infective Agents/chemistry/*pharmacology MH - Anti-Inflammatory Agents/chemistry/*pharmacology MH - Cells, Cultured MH - Dendritic Cells/cytology/*drug effects/immunology/microbiology MH - Healthy Volunteers MH - Humans MH - Immunity, Innate/drug effects MH - Interleukin-2/metabolism MH - Macrophages/cytology/*drug effects/immunology/microbiology MH - Mycobacterium bovis/*drug effects/pathogenicity MH - Origanum/*chemistry MH - Phagosomes/metabolism MH - Plant Extracts/chemistry/pharmacology MH - Transforming Growth Factor beta/metabolism MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC6398838 COIS- The authors have declared that no competing interests exist. EDAT- 2019/03/05 06:00 MHDA- 2019/12/04 06:00 PMCR- 2019/03/04 CRDT- 2019/03/05 06:00 PHST- 2018/11/08 00:00 [received] PHST- 2019/02/17 00:00 [accepted] PHST- 2019/03/05 06:00 [entrez] PHST- 2019/03/05 06:00 [pubmed] PHST- 2019/12/04 06:00 [medline] PHST- 2019/03/04 00:00 [pmc-release] AID - PONE-D-18-32196 [pii] AID - 10.1371/journal.pone.0213150 [doi] PST - epublish SO - PLoS One. 2019 Mar 4;14(3):e0213150. doi: 10.1371/journal.pone.0213150. eCollection 2019.