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

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., and Ketheesan, Natkunam (2018) Group G streptococcus induces an autoimmune carditis mediated by interleukin 17A and interferon γ in the Lewis rat model of rheumatic heart disease. Journal of Infectious Diseases, 218 (2). pp. 324-335.

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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.

Item ID: 56469
Item Type: Article (Research - C1)
ISSN: 1537-6613
Keywords: streptococcus pyogenes; group G streptococcus; acute rheumatic fever; rheumatic heart disease; rat autoimmune valvulitis
Copyright Information: Copyright © The Author(s) 2017.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Project Grant no. 1026753
Date Deposited: 05 Dec 2018 01:49
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 80%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 80%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 20%
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