{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:35:36Z","timestamp":1792852536223,"version":"4.5.0"},"reference-count":69,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1391\/17"],"award-info":[{"award-number":["1391\/17"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2230\/20"],"award-info":[{"award-number":["2230\/20"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,11,19]]},"abstract":"<jats:p>\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    is a gram-negative anaerobic bacterium linked to periodontal disease. Remarkably,\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    thrives in an inflamed environment rich in activated neutrophils. Toll-like receptor 2 (TLR2) recognition is required for\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    to evade innate immune killing; however, the mechanisms through which\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    uncouples host inflammation from bactericidal activity are only partially known. Since integrin activation and alternative signaling are implicated in\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    TLR2-mediated immune escape, we explored the role of CD47, a widely expressed integrin-associated protein known to suppress phagocytosis and implicated as an interacting partner with other innate immune receptors. We found that CD47 associates with TLR2, and blocking CD47 leads to decreased intracellular\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    survival in macrophages in a manner dependent on the bacterial major fimbria. In vivo, CD47 knock-out mice cleared\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    more efficiently than wild-type mice. Next, we found increased expression and secretion of the CD47 ligand thrombospondin-1 (TSP-1) following\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    infection. Secreted TSP-1 broadly protected\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    and other periodontitis-associated bacterial species from neutrophil bactericidal activity. Therefore, CD47-TLR2 cosignaling in response to\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    induces TSP-1 that in turn suppresses neutrophil activity, an effect that can explain how species such as\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    survive in an inflamed environment and cause dysbiosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2405534121","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T13:46:17Z","timestamp":1731505577000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":27,"title":["CD47 and thrombospondin-1 contribute to immune evasion by\n                    <i>Porphyromonas gingivalis<\/i>"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3797-0544","authenticated-orcid":false,"given":"Sarah","family":"Angabo","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-6879","authenticated-orcid":false,"given":"Karthikeyan","family":"Pandi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9497-6527","authenticated-orcid":false,"given":"Keren","family":"David","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orit","family":"Steinmetz","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasnaa","family":"Makkawi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Farhat","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luba","family":"Eli-Berchoer","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Darawshi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]},{"name":"Central Research Institute, Wakunaga Pharmaceutical Co. Ltd.","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-9893","authenticated-orcid":false,"given":"Gabriel","family":"Nussbaum","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3785"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v5i0.19804"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00359"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.12.7645"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011284"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8296"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900378"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000697"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.05.012"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12021"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803852105"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425883"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0113003"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.173"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01293-20"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900789"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00330"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2350"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004477"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.103024"},{"key":"e_1_3_4_21_2","first-page":"3","article-title":"Molecular functions of SIRP\u03b1 and its role in cancer","volume":"9","author":"Takahashi S.","year":"2018","unstructured":"S. Takahashi, Molecular functions of SIRP\u03b1 and its role in cancer. Biomed. Rep. 9, 3\u20137 (2018).","journal-title":"Biomed. Rep."},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084062"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3436"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-017-0601-x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.07.008"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18492"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep19684"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2012.01.002"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107618"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0195"},{"key":"e_1_3_4_31_2","first-page":"72","article-title":"Prevalence of periodontal disease, its association with systemic diseases and prevention","volume":"11","author":"Nazir M. A.","year":"2017","unstructured":"M. A. Nazir, Prevalence of periodontal disease, its association with systemic diseases and prevention. Int. J. Health Sci. (Qassim) 11, 72\u201380 (2017).","journal-title":"Int. J. Health Sci. (Qassim)"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1403089"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2023-330941"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-3827"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-26"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.4.2349"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02256-14"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv763"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345231222181"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.120362"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1080\/19768354.2020.1818618"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4025"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115107"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583644"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186179"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100683"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00079"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(00)01906-1"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2016.117"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005900"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12371"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00963-6"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1253025"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2873"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603146103"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1098321"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13203"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9060060"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12894"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg605"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1111"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17030385"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05712-4"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.120"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400853"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4283"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27773-8"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.565545"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2405534121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T16:14:59Z","timestamp":1733328899000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2405534121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":69,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2024,11,19]]}},"alternative-id":["10.1073\/pnas.2405534121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2405534121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]},"assertion":[{"value":"2024-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2405534121"}}