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

De Lisa Fairweather, Sylvia Frisancho-Kiss, Dolores B. Njoku, Jennifer F. Nyland, Ziya Kaya, Susy A. Yusung, Sarah E. Davis, J. Augusto Frisancho, Masheka A. Barrett, Noel R. Rose

Research output: Contribution to journalArticle

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-1β 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 B220low B cells were increased in the spleen of CR1/2-deficient mice during acute CVB3-induced myocarditis. These results show that expression of CR1/2 is not necessary for effective clearance of CVB3 infection, but prevents immune-mediated damage to the heart.

Original languageEnglish (US)
Pages (from-to)3516-3524
Number of pages9
JournalJournal of Immunology
Volume176
Issue number6
DOIs
StatePublished - Mar 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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