Author + information
- Carsten Skurk,
- Alexander Jenke,
- Moritz Becher,
- Alice Weithäuser,
- Karin Klingel,
- Heinz-Peter Schultheiss and
- Carmen Scheibenbogen
Adiponectin (APN) is an immunomodulatory adipocytokine that modulates outcome in patients with virus negative inflammatory cardiomyopathy and mice with autoimmune myocarditis. Moreover, APN controls antigen specific T cell responses and viral replication in hepatitis. Here, we investigated whether APN modulates cardiac inflammation and injury in CVB3 myocarditis.
Myocarditis was induced by CVB3 infection of APN-KO and WT mice. Viral load was determined by plaque assay and in situ hybridization. Gene expression was measured by qRT-PCR and FACS. Tissue histology was analyzed using H&E stained heart sections.
On day 7 p.i. APN-KO mice developed less severe subacute myocarditis with reduced viral load, diminished formation of inflammatory infiltrates and attenuated expression of immune cell markers NKp46, F4/80, CD3, CD4, CD8 and CD45 as well as immune response mediators IFNß, IFNγ, TNFα, IL-1β, IL-6, and IL-12. Moreover, the extent of necrotic lesions was less severe in hearts of APN-KO mice. In cultured cardiac myocytes APN had no influence on adhesion, uptake or replication of CVB3. Accordingly, in acute phase CVB3 myocarditis on day 3 p.i. cardiac viral load was unchanged in APN-KO mice. However, APN-KO mice displayed an intensified acute immune response in the heart designated by increased formation of inflammatory infiltrates and enhanced expression levels of macrophage and NK cell activation markers F4/80 and CD69 as well as immune response mediators IFNß, IFNγ, IL-12, TNFα and CCL2. At the same time, expression of the M2 macrophage polarization marker Mgl1 was reduced. Furthermore, NK cells from CVB3 infected APN-KO mice displayed increased IFNγ expression. Accordingly, APN inhibited TLR ligand induced IFNγ production in cultured NK cells.
Our observations indicate that APN promotes development of CVB3 myocarditis by modulating polarization of activated macrophages towards an anti-inflammatory M2 phenotype and influencing differentiation of NK cells resulting in a suppressed acute anti-viral immune response. Thus, in contrast to other models of inflammatory heart disease APN causes increased myocardial damage following CVB3 infection.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Myocarditis: Mechanistic Insights
Abstract Category: 23. Pericardial/Myocardial Disease
Presentation Number: 1207-148
- 2013 American College of Cardiology Foundation