Suppression of proinflammatory cytokines and induction of IL-10 in human monocytes after coxsackievirus B3 infection.
Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is accompanied by an intense mononuclear leukocyte infiltration. Because myocardial tissue damage may either result from viral infections or from a dysregulated immune response, the susceptibility of human monocytes and macrophages to CVB3 was examined in this study with regard to virus replication, virus persistence, and release of cytokines. Monocytes were infected by CVB3 as shown by the intracellular appearance of plus- and minus-strand viral RNA, which was also capable of persisting for more than 10 days. Fresh monocytes were not permissive for full virus replication whereas monocyte-derived macrophages yielded a low amount of new viruses, which led to cell death. Although CVB3 infection induced the mRNA for the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6, only little cytokine production occurred. When infected monocytes were stimulated in addition by lipopolysaccharides (LPS), cytokine production was partially suppressed. In striking contrast, IL-10 expression was strongly and persistently induced by CVB3 on the mRNA and the protein level. These data show a dysregulated cytokine response in CVB3-exposed human monocytes and macrophages, which is characterized by a suppression of proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid CVB3, causing chronic myocardiopathy.
Hofmann
P
P
Institute of Immunology, Philipps University Marburg, Marburg, Germany.
Schmidtke
M
M
Stelzner
A
A
Gemsa
D
D
D016923:Cell Death; D002454:Cell Differentiation; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D029822:Enterovirus B, Human; D006367:HeLa Cells; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D012333:RNA, Messenger; D012367:RNA, Viral / Q000032:analysis; D013997:Time Factors; D014779:Virus Replication
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012367:RNA, Viral; D016753:Interleukin-10