Abstract:
:Interleukin-10 (IL-10) suppresses the maturation and cytokine production of dendritic cells (DCs), key regulators of adaptive immunity, and prevents the activation and polarization of naïve T cells towards protective gamma interferon-producing effectors. We hypothesized that human cytomegalovirus (HCMV) utilizes its viral IL-10 homolog (cmvIL-10) to attenuate DC functionality, thereby subverting the efficient induction of antiviral immune responses. RNA and protein analyses demonstrated that the cmvIL-10 gene was expressed with late gene kinetics. Treatment of immature DCs (iDCs) with supernatant from HCMV-infected cultures inhibited both the lipopolysaccharide-induced DC maturation and proinflammatory cytokine production. These inhibitory effects were specifically mediated through the IL-10 receptor and were not observed when DCs were treated with supernatant of cells infected with a cmvIL-10-knockout mutant. Incubation of iDCs with recombinant cmvIL-10 recapitulated the inhibition of maturation. Furthermore, cmvIL-10 had pronounced long-term effects on those DCs that could overcome this inhibition of maturation. It enhanced the migration of mature DCs (mDCs) towards the lymph node homing chemokine but greatly reduced their cytokine production. The inability of mDCs to secrete IL-12 was maintained, even when they were restimulated by the activated T-cell signal CD40 ligand in the absence of cmvIL-10. Importantly, cmvIL-10 potentiates these anti-inflammatory effects, at least partially, by inducing endogenous cellular IL-10 expression in DCs. Collectively, we show that cmvIL-10 causes long-term functional alterations at all stages of DC activation.
journal_name
J Viroljournal_title
Journal of virologyauthors
Chang WL,Baumgarth N,Yu D,Barry PAdoi
10.1128/JVI.78.16.8720-8731.2004subject
Has Abstractpub_date
2004-08-01 00:00:00pages
8720-31issue
16eissn
0022-538Xissn
1098-5514pii
78/16/8720journal_volume
78pub_type
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
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更新日期:1976-10-01 00:00:00
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journal_title:Journal of virology
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更新日期:1979-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-03-01 00:00:00