α-Galactosylceramide protects mice from lethal Coxsackievirus B3 infection and subsequent myocarditis.
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.
Wu
C Y
CY
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.
Feng
Y
Y
Qian
G C
GC
Wu
J H
JH
Luo
J
J
Wang
Y
Y
Chen
G J
GJ
Guo
X K
XK
Wang
Z J
ZJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D029822:Enterovirus B, Human / Q000235:genetics / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D019562:Viral Load / Q000187:drug effects
D016207:Cytokines; D005699:Galactosylceramides; D012367:RNA, Viral; C493154:alpha-galactosylceramide