Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1beta, and immune complex deposition in the heart

The Journal of Immunology : Official Journal of the American Association of Immunologists
DeLisa FairweatherNoel R Rose

Abstract

Complement and complement receptors (CR) play a central role in immune defense by initiating the rapid destruction of invading microorganisms, amplifying the innate and adaptive immune responses, and mediating solubilization and clearance of immune complexes. Defects in the expression of C or CR have been associated with loss of tolerance to self proteins and the development of immune complex-mediated autoimmune diseases such as systemic lupus erythematosus. In this study, we examined the role of CR on coxsackievirus B3 (CVB3)-induced myocarditis using mice deficient in CR1/2. We found that CR1/2 deficiency significantly increased acute CVB3 myocarditis and pericardial fibrosis resulting in early progression to dilated cardiomyopathy and heart failure. The increase in inflammation was not due to increased viral replication, which was not significantly altered in the hearts of CR1/2-deficient mice, but was associated with increased numbers of macrophages, IL-1beta levels, and immune complex deposition in the heart. The complement regulatory protein, CR1-related gene/protein Y (Crry), was increased on cardiac macrophage populations, while immature B220(low) B cells were increased in the spleen of CR1/2-deficient mice during acute...Continue Reading

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Citations

Apr 11, 2008·Clinical and Vaccine Immunology : CVI·Dong LiuZhong-Xiang Niu
Jun 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ping ZhangMadeleine W Cunningham
May 11, 2019·Nature Reviews. Disease Primers·Heinz-Peter SchultheissSilvia G Priori
Jul 29, 2020·Reviews in Medical Virology·Ninaad Lasrado, Jay Reddy
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Mar 7, 2012·Expert Review of Clinical Immunology·DeLisa FairweatherLeslie T Cooper
Oct 31, 2009·Immunopharmacology and Immunotoxicology·Dong Liu, Zhong-Xiang Niu
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Feb 15, 2008·Critical Care Medicine·David ChenGuillermo Torre-Amione
Jun 3, 2021·Journal of Clinical Medicine·Angita JainDeLisa Fairweather
Oct 6, 2007·Current Opinion in Rheumatology
Aug 28, 2021·International Journal of Molecular Sciences·Katelyn A BrunoDeLisa Fairweather
Oct 13, 2009·Journal of Autoimmunity·Delisa Fairweather, Daniela Cihakova
Jan 30, 2010·Progress in Cardiovascular Diseases·Lori A Blauwet, Leslie T Cooper

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