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Clin Exp Immunol. 2010 Oct;162(1):178-87. doi: 10.1111/j.1365-2249.2010.04233.x. Epub 2010 Aug 19.

α-Galactosylceramide protects mice from lethal Coxsackievirus B3 infection and subsequent myocarditis.

Author information

1
Department of Microbiology and Parasitology, Division of Clinical Laboratory of the International Peace Maternity and Child Hospital, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Myocarditis is an inflammation of the myocardium which often follows virus infections. Coxsackievirus B3 (CVB3), as a marker of the enterovirus group, is one of the most important infectious agents of virus-induced myocarditis. Using a CVB3-induced myocarditis model, we show that injection α-galactosylceramide (α-GalCer), a ligand for invariant natural killer (NK) T (iNK T) cells, can protect the mice from viral myocarditis. After the systemic administration of α-GalCer in CVB3 infected mice, viral transcription and titres in mouse heart, sera and spleen were reduced, and the damage to the heart was ameliorated. This is accompanied by a better disease course with an improved weight loss profile. Compared with untreated mice, α-GalCer-treated mice showed high levels of interferon (IFN)-γ and interleukin (IL)-4, and reduced proinflammatory cytokines and chemokines in their cardiac tissue. Anti-viral immune response was up-regulated by α-GalCer. Three days after CVB3 infection, α-GalCer-administered mice had larger spleens. Besides NK T cells, more macrophages and CD8(+) T cells were found in these spleens. Upon stimulation with phorbol myristate acetate plus ionomycin, splenocytes from α-GalCer-treated mice produced significantly more cytokines [including IFN-γ, tumour necrosis factor-α, IL-4 and IL-10] than those from untreated mice. These data suggest that administration of α-GalCer during acute CVB3 infection is able to protect the mice from lethal myocarditis by local changes in inflammatory cytokine patterns and enhancement of anti-viral immune response at the early stage. α-GalCer is a potential candidate for viral myocarditis treatment. Our work supports the use of anti-viral treatment early to reduce the incidence of virus-mediated heart damage.

PMID:
20726989
PMCID:
PMC2990944
DOI:
10.1111/j.1365-2249.2010.04233.x
[Indexed for MEDLINE]
Free PMC Article

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