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These bacteria interact with several host cell receptors, one of which is the cell surface complement regulator CD46. In this study, we demonstrate that infection of epithelial cells with<jats:italic>S. pyogenes<\/jats:italic>leads to the shedding of CD46 at the same time as the bacteria induce apoptosis and cell death. Soluble CD46 attached to the streptococcal surface, suggesting that bacteria might bind available extracellular CD46 as a strategy to survive and avoid host defenses. The protective role of human CD46 was demonstrated in ex vivo whole-blood assays showing that the growth of<jats:italic>S. pyogenes<\/jats:italic>was enhanced in blood from mice expressing human CD46. Finally, in vivo experimental infection showed that bacteremia levels, arthritis frequency, and mortality were higher in CD46 transgenic mice than in nontransgenic mice. Taken together, these results argue that bacterial exploitation of human CD46 enhances bacterial survival and represents a novel pathogenic mechanism that contributes to the severity of group A streptococcal disease.<\/jats:p>","DOI":"10.1128\/iai.00109-08","type":"journal-article","created":{"date-parts":[[2008,6,24]],"date-time":"2008-06-24T00:55:18Z","timestamp":1214268918000},"page":"3951-3958","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["CD46 Contributes to the Severity of Group A Streptococcal Infection"],"prefix":"10.1128","volume":"76","author":[{"given":"Lena","family":"Lo\u0308vkvist","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Sjo\u0308linder","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahma","family":"Wehelie","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Aro","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Norrby-Teglund","sequence":"additional","affiliation":[{"name":"Center of Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Plant","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Beth","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.4.1871-1877.1999"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02664.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1008.031036"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.9.4385-4388.2004"},{"key":"e_1_3_2_6_2","first-page":"27","volume":"189","year":"2008","unstructured":"Chaussee, M. 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