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Although outer-membrane vesicles (OMVs) of Gram-negative bacteria are important players in microbiota\u2013host communication, the effect of S. copri-derived OMVs on immune cells is unknown. Macrophages engulf and eliminate foreign material and are conditioned by environmental signals to promote either homeostasis or inflammation. Thus, we aimed to explore the impact of S. copri-OMVs on human macrophages in vitro, employing THP-1 and monocyte-derived macrophage models. The uptake of DiO-labeled S. copri-OMVs into macrophages was monitored by confocal microscopy and flow cytometry. Furthermore, the effect of S. copri and S. copri-OMVs on the phenotype and cytokine secretion of na\u00efve (M0), pro-inflammatory (M1), and anti-inflammatory (M2) macrophages was analyzed by flow cytometry and ELISA, respectively. We show that S. copri-OMVs enter human macrophages through macropinocytosis and clathrin-dependent mechanisms. S. copri-OMVs, but not the parental bacterium, induced a dose-dependent increase in the expression of M1-related surface markers in M0 and M2 macrophages and activated the secretion of large amounts of pro-inflammatory cytokines in M1 macrophages. These results highlight an important role of S. copri-OMVs in promoting pro-inflammatory macrophage responses, which might contribute to systemic inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms26083630","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T10:05:51Z","timestamp":1744365951000},"page":"3630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Segatella copri Outer-Membrane Vesicles Are Internalized by Human Macrophages and Promote a Pro-Inflammatory Profile"],"prefix":"10.3390","volume":"26","author":[{"given":"Alison","family":"Sep\u00falveda-Pontigo","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Traslacional, Centro de Investigaci\u00f3n de Resiliencia a Pandemias, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Av. Rep\u00fablica 330, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0425-0812","authenticated-orcid":false,"given":"Karissa","family":"Ch\u00e1vez-Villacreses","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Traslacional, Centro de Investigaci\u00f3n de Resiliencia a Pandemias, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Av. Rep\u00fablica 330, Santiago 8370186, Chile"},{"name":"Programa de Doctorado en Biociencias Moleculares, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8057-8883","authenticated-orcid":false,"given":"Crist\u00f3bal","family":"Madrid-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Traslacional, Centro de Investigaci\u00f3n de Resiliencia a Pandemias, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Av. Rep\u00fablica 330, Santiago 8370186, Chile"},{"name":"Programa de Doctorado en Biociencias Moleculares, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Conejeros-Lillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Traslacional, Centro de Investigaci\u00f3n de Resiliencia a Pandemias, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Av. 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Rep\u00fablica 330, Santiago 8370186, Chile"},{"name":"Programa de Doctorado en Biotecnolog\u00eda, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A.","family":"Soto","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Traslacional, Centro de Investigaci\u00f3n de Resiliencia a Pandemias, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Av. 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Immunol., 11.","DOI":"10.3389\/fimmu.2020.00282"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.it.2021.09.006","article-title":"Host immunity and cellular responses to bacterial outer membrane vesicles","volume":"42","author":"Tiku","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri3837","article-title":"Immune modulation by bacterial outer membrane vesicles","volume":"15","author":"Ferrero","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mozaheb, N., and Mingeot-Leclercq, M.-P. (2020). Membrane Vesicle Production as a Bacterial Defense Against Stress. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.600221"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Marchant, P., Carre\u00f1o, A., Vivanco, E., Silva, A., Nevermann, J., Otero, C., Araya, E., Gil, F., Calder\u00f3n, I.L., and Fuentes, J.A. (2021). \u201cOne for All\u201d: Functional Transfer of OMV-Mediated Polymyxin B Resistance from Salmonella enterica sv. Typhi \u0394tolR and \u0394degS to Susceptible Bacteria. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.672467"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jan, A.T. (2017). Outer Membrane Vesicles (OMVs) of Gram-negative Bacteria: A Perspective Update. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01053"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Juodeikis, R., and Carding, S.R. (2022). Outer Membrane Vesicles: Biogenesis, Functions, and Issues. Microbiol. Mol. Biol. Rev., 86.","DOI":"10.1128\/mmbr.00032-22"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Stentz, R., Jones, E., Juodeikis, R., Wegmann, U., Guirro, M., Goldson, A.J., Brion, A., Booth, C., Sudhakar, P., and Brown, I.R. (2022). The Proteome of Extracellular Vesicles Produced by the Human Gut Bacteria Bacteroides thetaiotaomicron In Vivo Is Influenced by Environmental and Host-Derived Factors. Appl. Environ. Microbiol., 88.","DOI":"10.1128\/aem.00533-22"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Charpentier, L.A., Dolben, E.F., Hendricks, M.R., Hogan, D.A., Bomberger, J.M., and Stanton, B.A. (2023). Bacterial Outer Membrane Vesicles and Immune Modulation of the Host. Membranes, 13.","DOI":"10.3390\/membranes13090752"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105282","DOI":"10.1016\/j.neuint.2022.105282","article-title":"Secreted gingipains from Porphyromonas gingivalis increase permeability in human cerebral microvascular endothelial cells through intracellular degradation of tight junction proteins","volume":"154","author":"Nonaka","year":"2022","journal-title":"Neurochem. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.chom.2023.03.018","article-title":"Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles","volume":"31","author":"Hong","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/intimm\/dxy054","article-title":"Macrophages in inflammation, repair and regeneration","volume":"30","author":"Oishi","year":"2018","journal-title":"Int. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Austermann, J., Roth, J., and Barczyk-Kahlert, K. (2022). The Good and the Bad: Monocytes\u2019 and Macrophages\u2019 Diverse Functions in Inflammation. Cells, 11.","DOI":"10.3390\/cells11121979"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e12854","DOI":"10.1111\/cpr.12854","article-title":"Emerging role of targeting macrophages in rheumatoid arthritis: Focus on polarization, metabolism and apoptosis","volume":"53","author":"Yang","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2249152","DOI":"10.1080\/19490976.2023.2249152","article-title":"The curious case of Prevotella copri","volume":"15","author":"Abdelsalam","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, T., Long, W., Zhang, C., Liu, S., Zhao, L., and Hamaker, B.R. (2017). Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02995-4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.chom.2019.10.013","article-title":"Distinct Polysaccharide Utilization Profiles of Human Intestinal Prevotella copri Isolates","volume":"26","author":"Magnabosco","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1016\/j.chom.2023.09.013","article-title":"Extension of the Segatella copri complex to 13 species with distinct large extrachromosomal elements and associations with host conditions","volume":"31","author":"Pasolli","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature18646","article-title":"Human gut microbes impact host serum metabolome and insulin sensitivity","volume":"535","author":"Pedersen","year":"2016","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/jgh.16147","article-title":"A metagenomic study identifies a Prevotella copri enriched microbial profile associated with non-alcoholic steatohepatitis in subjects with obesity","volume":"38","author":"Torres","year":"2023","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2340487","DOI":"10.1080\/19490976.2024.2340487","article-title":"Effects of Prevotella copri on insulin, gut microbiota and bile acids","volume":"16","author":"Gong","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01202","DOI":"10.7554\/eLife.01202","article-title":"Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis","volume":"2","author":"Scher","year":"2013","journal-title":"eLife"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1136\/annrheumdis-2018-214514","article-title":"Prevotella copri in individuals at risk for rheumatoid arthritis","volume":"78","author":"Lesker","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/art.40003","article-title":"Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis","volume":"69","author":"Pianta","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1002\/art.39783","article-title":"Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine","volume":"68","author":"Maeda","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1136\/ard-2022-222881","article-title":"Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis","volume":"82","author":"Nii","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/s41419-019-1963-9","article-title":"Prevotella copri is associated with carboplatin-induced gut toxicity","volume":"10","author":"Yu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nevermann, J., Silva, A., Otero, C., Oyarz\u00fan, D.P., Barrera, B., Gil, F., Calder\u00f3n, I.L., and Fuentes, J.A. (2019). Identification of Genes Involved in Biogenesis of Outer Membrane Vesicles (OMVs) in Salmonella enterica Serovar Typhi. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00104"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lam, R.S., O\u2019Brien-Simpson, N.M., Holden, J.A., Lenzo, J.C., Fong, S.B., and Reynolds, E.C. (2016). Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158629"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1111\/cmi.12655","article-title":"Mechanisms of outer membrane vesicle entry into host cells","volume":"18","author":"Krachler","year":"2016","journal-title":"Cell. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pollak, C.N., Delpino, M.V., Fossati, C.A., and Baldi, P.C. (2012). Outer Membrane Vesicles from Brucella abortus Promote Bacterial Internalization by Human Monocytes and Modulate Their Innate Immune Response. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050214"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jconrel.2019.08.020","article-title":"Optimization of the method for analyzing endocytosis of fluorescently tagged molecules: Impact of incubation in the cell culture medium and cell surface wash with glycine-hydrochloric acid buffer","volume":"310","author":"Kamei","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1083\/jcb.121.1.61","article-title":"Clathrin and HA2 adaptors: Effects of potassium depletion, hypertonic medium, and cytosol acidification","volume":"121","author":"Hansen","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cecil, J.D., O\u2019brien-Simpson, N.M., Lenzo, J.C., Holden, J.A., Singleton, W., Perez-Gonzalez, A., Mansell, A., and Reynolds, E.C. (2017). Outer Membrane Vesicles Prime and Activate Macrophage Inflammasomes and Cytokine Secretion In Vitro and In Vivo. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01017"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Durant, L., Stentz, R., Noble, A., Brooks, J., Gicheva, N., Reddi, D., O\u2019connor, M.J., Hoyles, L., McCartney, A.L., and Man, R. (2020). Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease. Microbiome, 8.","DOI":"10.1186\/s40168-020-00868-z"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s12602-023-10058-6","article-title":"The Effect of Akkermansia muciniphila and Its Outer Membrane Vesicles on MicroRNAs Expression of Inflammatory and Anti-inflammatory Pathways in Human Dendritic Cells","volume":"16","author":"Mofrad","year":"2023","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"438","DOI":"10.21037\/atm.2016.08.53","article-title":"THP-1 cells as a model for human monocytes","volume":"4","author":"Bosshart","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, S., Lei, Q., Zou, X., and Ma, D. (2023). The role and mechanisms of gram-negative bacterial outer membrane vesicles in inflammatory diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1157813"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Catalan, E.A., Seguel-Fuentes, E., Fuentes, B., Aranguiz-Varela, F., Castillo-Godoy, D.P., Rivera-Asin, E., Bocaz, E., Fuentes, J.A., Bravo, D., and Schinnerling, K. (2024). Oral Pathobiont-Derived Outer Membrane Vesicles in the Oral\u2013Gut Axis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252011141"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gilmore, W.J., Johnston, E.L., Bitto, N.J., Zavan, L., O\u2019Brien-Simpson, N., Hill, A.F., and Kaparakis-Liaskos, M. (2022). Bacteroides fragilis outer membrane vesicles preferentially activate innate immune receptors compared to their parent bacteria. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.970725"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Krsek, D., Yara, D.A., Hrb\u00e1\u010dkov\u00e1, H., Daniel, O., Man\u010d\u00edkov\u00e1, A., Sch\u00fcller, S., and Bielaszewska, M. (2023). Translocation of outer membrane vesicles from enterohemorrhagic Escherichia coli O157 across the intestinal epithelial barrier. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1198945"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bhar, S., Zhao, G., Bartel, J.D., Sterchele, H., Del Mazo, A., Emerson, L.E., Edelmann, M.J., and Jones, M.K. (2022). Bacterial extracellular vesicles control murine norovirus infection through modulation of antiviral immune responses. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.909949"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33957","DOI":"10.1074\/jbc.M109.056309","article-title":"Translocation and Endocytosis for Cell-penetrating Peptide Internalization","volume":"284","author":"Jiao","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5054","DOI":"10.1128\/IAI.00299-10","article-title":"Uptake of Helicobacter pylori Outer Membrane Vesicles by Gastric Epithelial Cells","volume":"78","author":"Parker","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Jarzab, M., Posselt, G., Meisner-Kober, N., and Wessler, S. (2020). Helicobacter pylori-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis?. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091328"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41565-021-00858-8","article-title":"Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics","volume":"16","author":"Rennick","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/j.1462-5822.2005.00510.x","article-title":"Effects of the Escherichia coli toxin cytolysin A on mucosal immunostimulation via epithelial Ca2+ signalling and Toll-like receptor 4","volume":"7","author":"Soderblom","year":"2005","journal-title":"Cell Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.cell.2016.04.015","article-title":"Bacterial Outer Membrane Vesicles Mediate Cytosolic Localization of LPS and Caspase-11 Activation","volume":"165","author":"Vanaja","year":"2016","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1111\/j.1462-5822.2008.01228.x","article-title":"Clathrin-dependent entry of a gingipain adhesin peptide and Porphyromonas gingivalis into host cells","volume":"10","author":"Boisvert","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2351532","DOI":"10.1080\/19490976.2024.2351532","article-title":"Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-\u03baB signaling pathway","volume":"16","author":"Hao","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1038\/s41467-021-23683-y","article-title":"TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection","volume":"12","author":"Geng","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Skjesol, A., Yurchenko, M., B\u00f6sl, K., Gravastrand, C., Nilsen, K.E., Gr\u00f8vdal, L.M., Agliano, F., Patane, F., Lentini, G., and Kim, H. (2019). The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007684"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1021\/pr401227e","article-title":"Porphyromonas gingivalis Outer Membrane Vesicles Exclusively Contain Outer Membrane and Periplasmic Proteins and Carry a Cargo Enriched with Virulence Factors","volume":"13","author":"Veith","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jprot.2018.12.029","article-title":"Proteomic characterization of outer membrane vesicles from gut mucosa-derived fusobacterium nucleatum","volume":"195","author":"Liu","year":"2019","journal-title":"J. Proteom."},{"key":"ref_58","first-page":"1","article-title":"Prevotella Induces the Production of Th17 Cells in the Colon of Mice","volume":"2020","author":"Huang","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nrmicro3525","article-title":"Outer-membrane vesicles from Gram-negative bacteria: Biogenesis and functions","volume":"13","author":"Schwechheimer","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"102397","DOI":"10.1016\/j.autrev.2019.102397","article-title":"Macrophage M1\/M2 polarization and rheumatoid arthritis: A systematic review","volume":"18","author":"Tardito","year":"2019","journal-title":"Autoimmun. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1042\/CS20220531","article-title":"M1\/M2 macrophages and their overlaps\u2014Myth or reality?","volume":"137","author":"Strizova","year":"2023","journal-title":"Clin. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Fleetwood, A.J., Lee, M.K., Singleton, W., Achuthan, A., Lee, M.-C., O\u2019Brien-Simpson, N.M., Cook, A.D., Murphy, A.J., Dashper, S.G., and Reynolds, E.C. (2017). Metabolic Remodeling, Inflammasome Activation, and Pyroptosis in Macrophages Stimulated by Porphyromonas gingivalis and Its Outer Membrane Vesicles. Front. Cell Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00351"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.4049\/jimmunol.181.6.3733","article-title":"Macrophage Polarization in Bacterial Infections","volume":"181","author":"Benoit","year":"2008","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bcp.2019.03.029","article-title":"The many facets of macrophages in rheumatoid arthritis","volume":"165","author":"Siouti","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"173090","DOI":"10.1016\/j.ejphar.2020.173090","article-title":"Macrophage M1\/M2 polarization","volume":"877","author":"Yunna","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1038\/s41467-020-15831-7","article-title":"Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis","volume":"11","author":"Tajik","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Jones, E.J., Booth, C., Fonseca, S., Parker, A., Cross, K., Miquel-Clop\u00e9s, A., Hautefort, I., Mayer, U., Wileman, T., and Stentz, R. (2020). The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00057"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12974-023-02728-7","article-title":"Helicobacter pylori outer membrane vesicles induce astrocyte reactivity through nuclear factor-\u03baappa B activation and cause neuronal damage in vivo in a murine model","volume":"20","author":"Palacios","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Schaack, B., Mercier, C., Katby, M., Hannani, D., Vollaire, J., Robert, J.S., Caffaratti, C., Blanquet, F., Nicoud, O., and Josserand, V. (2024). Rapid Biodistribution of Fluorescent Outer-Membrane Vesicles from the Intestine to Distant Organs via the Blood in Mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031821"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/cei.12966","article-title":"The role of interleukin-6 signalling and its therapeutic blockage in skewing the T cell balance in rheumatoid arthritis","volume":"189","author":"Schinnerling","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kondo, N., Kuroda, T., and Kobayashi, D. (2021). Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010922"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"84","DOI":"10.18053\/jctres.02.201603.005","article-title":"The role of TNF-\u03b1 in rheumatoid arthritis: A focus on regulatory T cells","volume":"2","author":"Farrugia","year":"2016","journal-title":"J. Clin. Transl. Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yoshida, Y., and Tanaka, T. (2014). Interleukin 6 and Rheumatoid Arthritis. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/698313"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nm.3432","article-title":"Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis","volume":"20","author":"Komatsu","year":"2013","journal-title":"Nat. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12964-022-00924-1","article-title":"STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis","volume":"20","author":"Hou","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41584-018-0109-2","article-title":"Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis","volume":"15","author":"Chen","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.cyto.2015.08.260","article-title":"The role of cytokines in the pathogenesis of rheumatoid arthritis\u2014Practical and potential application of cytokines as biomarkers and targets of personalized therapy","volume":"76","author":"Brzustewicz","year":"2015","journal-title":"Cytokine"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/s41584-022-00790-8","article-title":"Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission","volume":"18","author":"Alivernini","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Johnston, E.L., Heras, B., Kufer, T.A., and Kaparakis-Liaskos, M. (2021). Detection of Bacterial Membrane Vesicles by NOD-Like Receptors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031005"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ajam-Hosseini, M., Akhoondi, F., Parvini, F., and Fahimi, H. (2024). Gram-negative bacterial sRNAs encapsulated in OMVs: An emerging class of therapeutic targets in diseases. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1305510"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3630\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:13:04Z","timestamp":1760029984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":80,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083630"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083630","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]}}}