{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:03:56Z","timestamp":1791918236422,"version":"4.3.4"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,2,14]]},"abstract":"<jats:p>\n                    Group A\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    (GAS) and other bacterial pathogens are known to interact with integrins as an initial step in a complex pathway of bacterial ingestion by host cells. Efficient GAS invasion depends on the interaction of bound fibronectin (Fn) with integrins and activation of integrin signaling. TGF-\u03b21 regulates expression of integrins, Fn, and other extracellular matrix proteins, and positively controls the integrin signaling pathway. Therefore, we postulated that TGF-\u03b21 levels could influence streptococcal invasion of mammalian cells. Pretreatment of HEp-2 cells with TGF-\u03b21 increased their capacity to ingest GAS when the bacteria expressed fibronectin-binding proteins (M1 or PrtF1). Western blots revealed significant induction of \u03b15 integrin and Fn expression by HEp-2 cells in response to TGF-\u03b21. Increased ingestion of streptococci by these cells was blocked by a specific inhibitor of the TGF-\u03b21 receptor I and antibodies directed against \u03b15 integrin and Fn, indicating that increased invasion depends on TGF-\u03b21 up-regulation of both the \u03b15 integrin and Fn. The capacity of TGF-\u03b21 to up-regulate integrin expression and intracellular invasion by GAS was reproduced in primary human tonsil fibroblasts, which could be a source of TGF-\u03b21 in chronically infected tonsils. The relationship between TGF-\u03b21 and GAS invasion was strengthened by the observation that TGF-\u03b21 production was stimulated in GAS-infected primary human tonsil fibroblasts. These findings suggest a mechanism by which GAS induce a cascade of changes in mammalian tissue leading to elevated expression of the \u03b15\u03b21 receptor, enhanced invasion, and increased opportunity for survival and persistence in their human host.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0506668103","type":"journal-article","created":{"date-parts":[[2006,2,7]],"date-time":"2006-02-07T22:18:40Z","timestamp":1139350720000},"page":"2380-2385","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["Streptococcal modulation of cellular invasion via TGF-\u03b21 signaling"],"prefix":"10.1073","volume":"103","author":[{"given":"Beinan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School, 1460 Mayo Memorial Building, MMC 196, 420 Delaware Street Southeast, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School, 1460 Mayo Memorial Building, MMC 196, 420 Delaware Street Southeast, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Southern","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School, 1460 Mayo Memorial Building, MMC 196, 420 Delaware Street Southeast, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick P.","family":"Cleary","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School, 1460 Mayo Memorial Building, MMC 196, 420 Delaware Street Southeast, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,2,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.108.5.1180"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.104.4.911"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199705000-00016"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.5.2532"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00576-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.25.12115"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.4593-4601.1998"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050587897"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2000.00040.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00618.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01097.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.10.5823-5830.2003"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1273rev"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00432-X"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.183"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117004"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3177"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.10.130"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204996"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.4049\/jimmunol.143.4.1142","volume":"143","author":"Lafyatis R.","year":"1989","unstructured":"R. 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