Group G streptococcus induces an autoimmune carditis mediated by interleukin 17A and interferon γ in the Lewis rat model of rheumatic heart disease

Journal Publication ResearchOnline@JCU
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
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.

Journal

Journal of Infectious Diseases

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Volume

218

ISBN/ISSN

1537-6613

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Issue

2

Pages Count

12

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Publisher

Oxford University Press

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N/A

DOI

10.1093/infdis/jix637