{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T01:52:01Z","timestamp":1778723521825,"version":"3.51.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Streptococcus pyogenes (or group A streptococcus [GAS]) is a major human pathogen causing infections, such as tonsillitis, erysipelas, and sepsis. Several GAS strains bind host complement regulator factor H (CFH) via its domain 7 and, thereby, evade complement attack and C3b-mediated opsonophagocytosis. Importance of CFH binding for survival of GAS has been poorly studied because removal of CFH from plasma or blood causes vigorous complement activation, and specific inhibitors of the interaction have not been available. In this study, we found that activation of human complement by different GAS strains (n = 38) correlated negatively with binding of CFH via its domains 5\u20137. The importance of acquisition of host CFH for survival of GAS in vitro was studied next by blocking the binding with recombinant CFH5\u20137 lacking the regulatory domains 1\u20134. Using this fragment in full human blood resulted in death or radically reduced multiplication of all of the studied CFH-binding GAS strains. To study the importance of CFH binding in vivo (i.e., for pathogenesis of streptococcal infections), we used our recent finding that GAS binding to CFH is diminished in vitro by polymorphism 402H, which is also associated with age-related macular degeneration. We showed that allele 402H is suggested to be associated with protection from erysipelas (n = 278) and streptococcal tonsillitis (n = 209) compared with controls (n = 455) (p &amp;lt; 0.05). Taken together, the bacterial in vitro survival data and human genetic association revealed that binding of CFH is important for pathogenesis of GAS infections and suggested that inhibition of CFH binding can be a novel therapeutic approach in GAS infections.<\/jats:p>","DOI":"10.4049\/jimmunol.1102545","type":"journal-article","created":{"date-parts":[[2011,12,3]],"date-time":"2011-12-03T20:23:45Z","timestamp":1322943825000},"page":"426-435","source":"Crossref","is-referenced-by-count":41,"title":["Acquisition of Complement Factor H Is Important for Pathogenesis of <i>Streptococcus pyogenes<\/i> Infections: Evidence from Bacterial In Vitro Survival and Human Genetic Association"],"prefix":"10.1093","volume":"188","author":[{"given":"Karita","family":"Haapasalo","sequence":"first","affiliation":[{"name":"Department of Bacteriology and Immunology and Infection Biology Program, Haartman Institute, University of Helsinki , FIN-00290 Helsinki ,","place":["Finland"]},{"name":"HUSLAB, Helsinki University Central Hospital Laboratory , FIN-00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaana","family":"Vuopio","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, National Institute for Health and Welfare , FIN-00271 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaana","family":"Syrj\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tampere University Central Hospital , FIN-33521 Tampere ,","place":["Finland"]},{"name":"School of Medicine, University of Tampere , FIN-33520 Tampere ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jari","family":"Suvilehto","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology and Infection Biology Program, Haartman Institute, University of Helsinki , FIN-00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satu","family":"Massinen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haartman Institute, University of Helsinki , FIN-00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matti","family":"Karppelin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tampere University Central Hospital , FIN-33521 Tampere ,","place":["Finland"]},{"name":"School of Medicine, University of Tampere , FIN-33520 Tampere ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irma","family":"J\u00e4rvel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haartman Institute, University of Helsinki , FIN-00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seppo","family":"Meri","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology and Infection Biology Program, Haartman Institute, University of Helsinki , FIN-00290 Helsinki ,","place":["Finland"]},{"name":"HUSLAB, Helsinki University Central Hospital Laboratory , FIN-00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juha","family":"Kere","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haartman Institute, University of Helsinki , FIN-00290 Helsinki ,","place":["Finland"]},{"name":"Department of Biosciences and Nutrition, Karolinska Institutet , SE-14183 Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T Sakari","family":"Jokiranta","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology and Infection Biology Program, Haartman Institute, University of Helsinki , FIN-00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2025032409420579000_r1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/CMR.13.3.470","article-title":"Pathogenesis of group A streptococcal infections","volume":"13","author":"Cunningham","year":"2000","journal-title":"Clin. 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Head Neck Surg."},{"key":"2025032409420579000_r5","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1111\/j.1462-5822.2007.00981.x","article-title":"Macrophage complement receptors and pathogen clearance","volume":"9","author":"van Lookeren Campagne","year":"2007","journal-title":"Cell. Microbiol."},{"key":"2025032409420579000_r6","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/eji.201040355","article-title":"Complement fragments C3a and C5a: the salt and pepper of the immune response","volume":"40","author":"Sacks","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"2025032409420579000_r7","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1073\/pnas.75.8.3948","article-title":"Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins","volume":"75","author":"Schreiber","year":"1978","journal-title":"Proc. Natl. Acad. Sci. 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Vis."},{"key":"2025032409420579000_r33","doi-asserted-by":"crossref","first-page":"24713","DOI":"10.1074\/jbc.M605083200","article-title":"His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form","volume":"281","author":"Clark","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025032409420579000_r34","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.4049\/jimmunol.178.6.3831","article-title":"Y402H polymorphism of complement factor H affects binding affinity to C-reactive protein","volume":"178","author":"Laine","year":"2007","journal-title":"J. Immunol."},{"key":"2025032409420579000_r35","doi-asserted-by":"crossref","first-page":"30451","DOI":"10.1074\/jbc.M803648200","article-title":"Complement factor H binds to denatured rather than to native pentameric C-reactive protein","volume":"283","author":"Hakobyan","year":"2008","journal-title":"J. Biol. 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