Group G Streptococcus Induces an Autoimmune Carditis Mediated by Interleukin 17A and Interferon γ in the Lewis Rat Model of Rheumatic Heart Disease. (9th December 2017)

• Record Type: Journal Article
• Authors: Sikder, Suchandan; Williams, Natasha L; Sorenson, Alanna E; Alim, Md A; Vidgen, Miranda E; Moreland, Nicole J; Rush, Catherine M; Simpson, Robert S; Govan, Brenda L; Norton, Robert E; Cunningham, Madeleine W; McMillan, David J; Sriprakash, Kadaba S; Ketheesan, Natkunam
• Is Part Of: Journal of infectious diseases. Volume 218:Number 2(2018)
• Page Start: 324
• Page End: 335
• Publication Date: 2017-12-09
• Subjects: Streptococcus pyogenes -- group G streptococcus -- acute rheumatic fever -- rheumatic heart disease -- rat autoimmune valvulitis; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix637
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune sequelae of group A streptococcal infections. Here we provide experimental evidence that group G Streptococcus may also induce and/or exacerbate ARF/RHD. Abstract: Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection. Both antibody and T-cell responses against immunodominant GAS virulence factors, including M protein, cross-react with host tissue proteins, triggering an inflammatory response leading to permanent heart damage. However, in some ARF/RHD-endemic regions, throat carriage of GAS is low. Because Streptococcus dysgalactiae subspecies equisimilis organisms, also known as β-hemolytic group C streptococci and group G streptococci (GGS), also express M protein, we postulated that streptococci other than GAS may have the potential to initiate or exacerbate ARF/RHD. Using a model initially developed to investigate the uniquely human disease of ARF/RHD, we have discovered that GGS causes interleukin 17A/interferon γ–induced myocarditis and valvulitis, hallmarks of ARF/RHD. Remarkably the histological, immunological, and functional changes in the hearts of rats exposed to GGS are identical to those exposed to GAS. Furthermore, antibody cross-reactivity to cardiac myosin was comparable in both GGS- and GAS-exposed animals, providing additional evidence that GGS can induce and/or exacerbate ARF/RHD.