Antigen‐presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis

Abstract

Coxsackievirus B3 (CVB3)‐infection is a frequent cause of acute myocarditis, which may result in chronic myocarditis and virus persistence. Investigation of the initial immune responses to CVB3 may shed light on the mechanisms that contribute to ongoing disease. DCs, as key professional APCs, were investigated in two MHC‐matched hosts: while C57BL/6 mice are resistant to chronic CVB3‐myocarditis, the A.BY/SnJ mouse strain exhibits susceptibility. DC maturation and activation were critically impaired in A.BY/SnJ mice, as reflected by the failure of DCs to induce co‐stimulatory molecules and cytokine/chemokine responses. MHC class I‐restricted antigen presentation via the cross‐presentation pathway was also affected in DCs from A.BY/SnJ mice. DC maturation involves the accumulation of DC aggresome‐like induced structures (DALISs) and the transient storage of defective ribosomal products (DRiPs). DCs from A.BY/SnJ mice showed permanent DALIS accumulation; the detection of poly‐ubiquitinylated CVB3 proteins in these DALISs suggested a limitation in the MHC class I antigenic supply in this host. In conclusion, ongoing chronic disease in A.BY/SnJ mice due to a failure to clear the virus may be attributed to defects in DC maturation/activation and DC MHC class I antigen processing.

Wild-type coxsackievirus infection dramatically alters the abundance, heterogeneity, and immunostimulatory capacity of conventional dendritic cells in vivo

“…Overall, the 3 major subsets of cDCs in the spleen displayed an activated phenotype within 48 hrs of CVB3 infection, and strongly up-regulated the costimulatory molecule CD86. A recent study examined changes in CD11c + DC phenotype in vivo at 36 hrs post CVB3 infection, but failed to detect a substantial change in MHC class I and II expression at this time point (Rahnefeld et al , 2011). In contrast, our detailed analysis of cDC subsets revealed that CD8α + DCs up-regulate these MHC molecules by 48 hrs p.i.…”

Ubiquitin-Like Protein ISG15 (Interferon-Stimulated Gene of 15 kDa) in Host Defense Against Heart Failure in a Mouse Model of Virus-Induced Cardiomyopathy

“…For immune cell-based assays, splenocytes were obtained as described. 28 For natural killer (NK) cell assays, the NK cell containing cell fraction was enriched by Ficoll density gradient centrifugation (Biocoll, Biochrom) and magnetic cell separation (MACS, Miltenyi).…”

Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy

“…Interestingly, a subset of DCs expressing TLR3, as well as higher quantities of IL-10 and the proinflammatory cytokines IL-6 and TNF- α , has been shown to be beneficial in the prevention of chronic CVB3 myocarditis [46]. Furthermore, a defect in DCs maturation/activation and DCs MHC class I antigen processing is associated with failure in viral clearance leading to ongoing chronic disease [47]. …”