{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:34:35Z","timestamp":1792798475866,"version":"4.5.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | National Institute of Dental and Craniofacial Research","award":["DE029612, DE029492"],"award-info":[{"award-number":["DE029612, DE029492"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"crossref"}]},{"name":"HHS | NIH | National Institute of Dental and Craniofacial Research","award":["DE028252"],"award-info":[{"award-number":["DE028252"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI167974"],"award-info":[{"award-number":["AI167974"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI130055"],"award-info":[{"award-number":["AI130055"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2025,3,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The commensal\n                      <jats:italic>Streptococcus sanguinis<\/jats:italic>\n                      is highly prevalent in the oral cavity and characterized for its ability to inhibit growth of oral pathogens. Like many other cell types, streptococci produce extracellular membrane vesicles (EMVs), which contain specific molecular cargo and facilitate interactions with host cells. We previously demonstrated that EMVs from\n                      <jats:italic>S. sanguinis<\/jats:italic>\n                      are internalized by gingival epithelial cells (GECs) without causing cell death. Our aim is to characterize the effects of vesicles on eukaryotic cells. Microscopy studies of gingival epithelial cells inoculated with EMVs from wild-type and specific deletion mutants show differential uptake, with decreased uptake of \u0394SSA1099 EMVs and increased uptake of \u0394SSA1882 EMVs relative to SK36 EMVs. However, EMVs from wild-type and deletion mutants showed similar patterns in cytokine and chemokine secretion. Transcriptomic analysis of gingival epithelial cells inoculated with SK36 EMVs showed a downregulation of genes implicated in apoptosis as well as interferon signaling, while showing an upregulation of genes involved in cytokine production. Gelatin zymography results show that SK36 EMVs have a contrasting result on production of MMP2\/9; MMP2 production is decreased while MMP9 is increased by 48 hours post-inoculation (hpi). Dual-inoculation studies demonstrate that prior internalization of\n                      <jats:italic>S. sanguinis<\/jats:italic>\n                      EMVs protects gingival epithelial cells from exposure to pathobiont\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      outer membrane vesicles (OMVs), preventing dissociation and cell death. Our overall findings suggest that\n                      <jats:italic>S. sanguinis<\/jats:italic>\n                      EMVs trigger an immune response on gingival epithelial cells; however, this response suggests inhibition of some immune signaling pathways. Our results highlight an important role in commensalism, in which a microbe induces an immune response but avoids damage to host cells, thus discouraging infection by pathobionts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00535-24","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T09:00:38Z","timestamp":1739955638000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Immunostimulatory effects of\n                    <i>Streptococcus sanguinis<\/i>\n                    extracellular membrane vesicles protect oral gingival epithelial cells from periodontal pathobiont damage"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6340-7260","authenticated-orcid":false,"given":"Emily","family":"Helliwell","sequence":"first","affiliation":[{"name":"Division of Biomaterial and Biomedical Sciences, School of Dentistry, Oregon Health & Science University","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1897-5693","authenticated-orcid":true,"given":"Isabella","family":"Rauch","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Nice","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3464-0490","authenticated-orcid":true,"given":"Justin","family":"Merritt","sequence":"additional","affiliation":[{"name":"Division of Biomaterial and Biomedical Sciences, School of Dentistry, Oregon Health & Science University","place":["Portland, USA"]},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-8310","authenticated-orcid":true,"given":"Jens","family":"Kreth","sequence":"additional","affiliation":[{"name":"Division of Biomaterial and Biomedical Sciences, School of Dentistry, Oregon Health & Science University","place":["Portland, USA"]},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0089-x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.671968"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00276-08"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.686479"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.gpp3-0052-2018"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522149113"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-020-0598-2"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-020-0592-8"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-023-01456-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00432"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/501361"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.9.4925-4935.2003"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00010"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9112380"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.23.8144"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.2.503-510.1996"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00875-5"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12608"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.846192"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03288-22"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00299-10"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12272"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/35055027"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2014.2677"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183329"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.047"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.101"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20230063"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.27902"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2024.156652"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.615603"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301357"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051x.1995.tb00831.x"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0757.2003.03107.x"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1167160"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.2003.00301.x"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep33638"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12059"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01657-21"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00535-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00535-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T07:28:10Z","timestamp":1743665290000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00535-24"}},"subtitle":[],"editor":[{"given":"Nancy E.","family":"Freitag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,11]]}},"alternative-id":["10.1128\/iai.00535-24"],"URL":"https:\/\/doi.org\/10.1128\/iai.00535-24","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]},"assertion":[{"value":"2024-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00535-24"}}