Group G streptococcus induces an autoimmune IL-17A/IFN-γ mediated carditis in the Lewis rat model of Rheumatic Heart Disease.

Research paper by Suchandan S Sikder, Natasha L NL Williams, Alanna E AE Sorenson, Md A MA Alim, Miranda E ME Vidgen, Nicole J NJ Moreland, Catherine M CM Rush, Robert S RS Simpson, Brenda L BL Govan, Robert E RE Norton, Madeleine W MW Cunningham, David J DJ McMillan, Kadaba S KS Sriprakash, Natkunam N Ketheesan

Indexed on: 14 Dec '17Published on: 14 Dec '17Published in: The Journal of infectious diseases


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. As Streptococcus dysgalactiae subspecies equisimilis (SDSE), also known as β-hemolytic groups C and G streptococci (GCS/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 now discovered that GGS does indeed causes IL-17A/IFN-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.