{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T04:49:07Z","timestamp":1744174147291,"version":"3.40.3"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"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":[[2011,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Host immunogenetic variations strongly influence the severity of group A streptococcus sepsis by modulating responses to streptococcal superantigens (Strep-SAgs). Although HLA-II\u2013DR15\/DQ6 alleles strongly protect against severe sepsis, HLA-II\u2013DR14\/DR7\/DQ5 alleles significantly increase the risk for toxic shock syndrome. We found that, regardless of individual variations in TCR-V\u03b2 repertoires, the presentation of Strep-SAgs by the protective HLA-II\u2013DR15\/DQ6 alleles significantly attenuated proliferative responses to Strep-SAgs, whereas their presentation by the high-risk alleles augmented it. Importantly, HLA-II variations differentially polarized cytokine responses to Strep-SAgs: the presentation of Strep-SAgs by HLA-II\u2013DR15\/DQ6 alleles elicited significantly higher ratios of anti-inflammatory cytokines (e.g., IL-10) to proinflammatory cytokines (e.g., IFN-\u03b3) than did their presentation by the high-risk HLA-II alleles. Adding exogenous rIL-10 significantly attenuated responses to Strep-SAgs presented by the high-risk HLA-II alleles but did not completely block the response; instead, it reduced it to a level comparable to that seen when these superantigens were presented by the protective HLA-II alleles. Furthermore, adding neutralizing anti\u2013IL-10 Abs augmented Strep-SAg responses in the presence of protective HLA-II alleles to the same level as (but no higher than) that seen when the superantigens were presented by the high-risk alleles. Our findings provide a molecular basis for the role of HLA-II allelic variations in modulating streptococcal sepsis outcomes and suggest the presence of an internal control mechanism that maintains superantigen responses within a defined range, which helps to eradicate the infection while attenuating pathological inflammatory responses that can inflict more harm than the infection itself.<\/jats:p>","DOI":"10.4049\/jimmunol.1002057","type":"journal-article","created":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T01:55:06Z","timestamp":1296525306000},"page":"3156-3163","source":"Crossref","is-referenced-by-count":21,"title":["Individual Genetic Variations Directly Effect Polarization of Cytokine Responses to Superantigens Associated with Streptococcal Sepsis: Implications for Customized Patient Care"],"prefix":"10.1093","volume":"186","author":[{"given":"Mohammed M","family":"Nooh","sequence":"first","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center , Cincinnati, OH 45220"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Cairo University , Cairo 11562 ,","place":["Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suba","family":"Nookala","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center , Cincinnati, OH 45220"},{"name":"Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati , Cincinnati, OH 45267"},{"name":"Midwest Center for Emerging Infectious Diseases, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Kansal","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center , Cincinnati, OH 45220"},{"name":"Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati , Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malak","family":"Kotb","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center , Cincinnati, OH 45220"},{"name":"Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati , Cincinnati, OH 45267"},{"name":"Midwest Center for Emerging Infectious Diseases, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,3,1]]},"reference":[{"key":"2025032411111952300_r1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1146\/annurev.med.54.101601.152346","article-title":"The influence of HLA genotype on AIDS","volume":"54","author":"Carrington","year":"2003","journal-title":"Annu. 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Microbiol."},{"key":"2025032411111952300_r15","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.molmed.2005.02.001","article-title":"Uncovering the mysteries of invasive streptococcal diseases","volume":"11","author":"Chhatwal","year":"2005","journal-title":"Trends Mol. Med."},{"key":"2025032411111952300_r16","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. Microbiol. Rev."},{"volume-title":"The Reemergence of Severe Group A Streptococcal Disease: An Evolutionary Perspective.","year":"1998","author":"Low","key":"2025032411111952300_r17"},{"key":"2025032411111952300_r18","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3201\/eid1410.071660","article-title":"Rise and persistence of global M1T1 clone of Streptococcus pyogenes","volume":"14","author":"Aziz","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"2025032411111952300_r19","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1128\/IAI.68.6.3523-3534.2000","article-title":"Genetic relatedness and superantigen expression in group A streptococcus serotype M1 isolates from patients with severe and nonsevere invasive diseases","volume":"68","author":"Chatellier","year":"2000","journal-title":"Infect. Immun."},{"key":"2025032411111952300_r20","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1086\/340576","article-title":"A comparison of group A streptococci from invasive and uncomplicated infections: are virulent clones responsible for serious streptococcal infections?","volume":"185","author":"Johnson","year":"2002","journal-title":"J. Infect. Dis."},{"key":"2025032411111952300_r21","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1128\/IAI.67.4.1871-1877.1999","article-title":"Risk factors in the pathogenesis of invasive group A streptococcal infections: role of protective humoral immunity","volume":"67","author":"Basma","year":"1999","journal-title":"Infect. Immun."},{"key":"2025032411111952300_r22","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1086\/651019","article-title":"Dissection of the molecular basis for hypervirulence of an in vivo-selected phenotype of the widely disseminated M1T1 strain of group A Streptococcus bacteria","volume":"201","author":"Kansal","year":"2010","journal-title":"J. Infect. Dis."},{"key":"2025032411111952300_r23","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrmicro771","article-title":"The pathogenesis of streptococcal infections: from tooth decay to meningitis","volume":"1","author":"Mitchell","year":"2003","journal-title":"Nat. Rev. Microbiol."},{"key":"2025032411111952300_r24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jaci.2007.06.005","article-title":"Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets","volume":"120","author":"Nizet","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032411111952300_r25","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1128\/CMR.8.3.411","article-title":"Bacterial pyrogenic exotoxins as superantigens","volume":"8","author":"Kotb","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"2025032411111952300_r26","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1128\/iai.65.12.5209-5215.1997","article-title":"Differential induction of Th1 versus Th2 cytokines by group A streptococcal toxic shock syndrome isolates","volume":"65","author":"Norrby-Teglund","year":"1997","journal-title":"Infect. 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Eng."},{"key":"2025032411111952300_r37","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/gm52","article-title":"Genetics and Genomics of Infectious Diseases: advancing our understanding of host\/pathogens and their interactions","volume":"1","author":"Yang","year":"2009","journal-title":"Genome Med."},{"key":"2025032411111952300_r38","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1172\/JCI38111","article-title":"Human genetics of infectious diseases: between proof of principle and paradigm","volume":"119","author":"Alca\u00efs","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2025032411111952300_r39","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.4049\/jimmunol.178.5.3076","article-title":"HLA transgenic mice provide evidence for a direct and dominant role of HLA class II variation in modulating the severity of streptococcal sepsis","volume":"178","author":"Nooh","year":"2007","journal-title":"J. Immunol."},{"key":"2025032411111952300_r40","doi-asserted-by":"crossref","first-page":"35281","DOI":"10.1074\/jbc.M605544200","article-title":"Streptococcal mitogenic exotoxin, SmeZ, is the most susceptible M1T1 streptococcal superantigen to degradation by the streptococcal cysteine protease, SpeB","volume":"281","author":"Nooh","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025032411111952300_r41","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1128\/JB.187.10.3311-3318.2005","article-title":"Mosaic prophages with horizontally acquired genes account for the emergence and diversification of the globally disseminated M1T1 clone of Streptococcus pyogenes","volume":"187","author":"Aziz","year":"2005","journal-title":"J. Bacteriol."},{"key":"2025032411111952300_r42","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1128\/iai.60.2.701-705.1992","article-title":"Distinct T-cell receptor V beta gene usage by human T lymphocytes stimulated with the streptococcal pyrogenic exotoxins and pep M5 protein","volume":"60","author":"Tomai","year":"1992","journal-title":"Infect. Immun."},{"key":"2025032411111952300_r43","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1046\/j.1365-2249.2003.02203.x","article-title":"Bacterial superantigens","volume":"133","author":"Proft","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"2025032411111952300_r44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.0300-9475.2004.01404.x","article-title":"Interplay between superantigens and immunoreceptors","volume":"59","author":"Petersson","year":"2004","journal-title":"Scand. J. Immunol."},{"key":"2025032411111952300_r45","first-page":"1","article-title":"Streptococcal superantigens","volume":"93","author":"Proft","year":"2007","journal-title":"Chem. Immunol. Allergy"},{"key":"2025032411111952300_r46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0092-8674(89)90980-X","article-title":"The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice","volume":"56","author":"White","year":"1989","journal-title":"Cell"},{"key":"2025032411111952300_r47","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1006\/bbrc.1994.1779","article-title":"Signalling via MHC class II molecules selectively induces IL-1 beta over IL-1 receptor antagonist gene expression","volume":"201","author":"al-Daccak","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025032411111952300_r48","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1128\/iai.65.10.4190-4198.1997","article-title":"Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM","volume":"65","author":"Cole","year":"1997","journal-title":"Infect. Immun."},{"key":"2025032411111952300_r49","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0198-8859(98)00131-1","article-title":"Ligation of MHC class II molecules differentially upregulates TNF beta gene expression in B cell lines of different MHC class II haplotypes","volume":"60","author":"Guo","year":"1999","journal-title":"Hum. Immunol."},{"key":"2025032411111952300_r50","doi-asserted-by":"crossref","first-page":"5025","DOI":"10.1128\/iai.60.12.5025-5029.1992","article-title":"Relative abilities of distinct isotypes of human major histocompatibility complex class II molecules to bind streptococcal pyrogenic exotoxin types A and B","volume":"60","author":"Imanishi","year":"1992","journal-title":"Infect. Immun."},{"key":"2025032411111952300_r51","doi-asserted-by":"crossref","first-page":"6892","DOI":"10.1073\/pnas.94.13.6892","article-title":"Selective binding of bacterial toxins to major histocompatibility complex class II-expressing cells is controlled by invariant chain and HLA-DM","volume":"94","author":"Lavoie","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411111952300_r52","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1002\/eji.1830260917","article-title":"Synergistic effect between CD40 and class II signals overcome the requirement for class II dimerization in superantigen-induced cytokine gene expression","volume":"26","author":"Mehindate","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"2025032411111952300_r53","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1084\/jem.182.5.1573","article-title":"Cross-linking of major histocompatibility complex class II molecules by staphylococcal enterotoxin A superantigen is a requirement for inflammatory cytokine gene expression","volume":"182","author":"Mehindate","year":"1995","journal-title":"J. Exp. Med."},{"key":"2025032411111952300_r54","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1002\/1521-4141(200209)32:9<2570::AID-IMMU2570>3.0.CO;2-E","article-title":"Differential presentation of group A streptococcal superantigens by HLA class II DQ and DR alleles","volume":"32","author":"Norrby-Teglund","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"2025032411111952300_r55","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4049\/jimmunol.144.1.226","article-title":"Effect of isotypes and allelic polymorphism on the binding of staphylococcal exotoxins to MHC class II molecules","volume":"144","author":"Scholl","year":"1990","journal-title":"J. Immunol."},{"key":"2025032411111952300_r56","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa063842","article-title":"Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412","volume":"355","author":"Suntharalingam","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2025032411111952300_r57","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1097\/00003246-199608000-00023","article-title":"A personal experience with SIRS and MODS","volume":"24","author":"Bone","year":"1996","journal-title":"Crit. Care Med."},{"key":"2025032411111952300_r58","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/0732-8893(90)90006-H","article-title":"Cytokines and septic shock","volume":"13","author":"Calandra","year":"1990","journal-title":"Diagn. Microbiol. Infect. Dis."},{"issue":"6","key":"2025032411111952300_r59","doi-asserted-by":"crossref","first-page":"321S","DOI":"10.1378\/chest.112.6_Supplement.321S","article-title":"Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock","volume":"112","author":"Dinarello","year":"1997","journal-title":"Chest"},{"key":"2025032411111952300_r60","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/01.CCM.0000104950.52577.97","article-title":"Plasma interferon-gamma and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock","volume":"32","author":"Bjerre","year":"2004","journal-title":"Crit. Care Med."},{"key":"2025032411111952300_r61","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.19.1.683","article-title":"Interleukin-10 and the interleukin-10 receptor","volume":"19","author":"Moore","year":"2001","journal-title":"Annu. Rev. Immunol."},{"issue":"12","key":"2025032411111952300_r62","doi-asserted-by":"crossref","first-page":"S468","DOI":"10.1097\/01.CCM.0000186268.53799.67","article-title":"Biology of interleukin-10 and its regulatory roles in sepsis syndromes","volume":"33","author":"Scumpia","year":"2005","journal-title":"Crit. Care Med."},{"key":"2025032411111952300_r63","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1084\/jem.174.4.915","article-title":"Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression","volume":"174","author":"de Waal Malefyt","year":"1991","journal-title":"J. Exp. Med."},{"key":"2025032411111952300_r64","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1084\/jem.177.2.547","article-title":"Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia","volume":"177","author":"G\u00e9rard","year":"1993","journal-title":"J. Exp. Med."},{"key":"2025032411111952300_r65","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1084\/jem.177.4.1205","article-title":"Interleukin 10 protects mice from lethal endotoxemia","volume":"177","author":"Howard","year":"1993","journal-title":"J. Exp. 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