IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence

Il-10 is an anti-inflammatory cytokine that regulates the extent of host immunity to infection by exerting suppressive effects on different cell types. herpes viruses induce il-10 to modulate the virus-host balance towards their own benefit,resulting in prolonged virus persistence. to define the cellular and molecular players involved in il-10 modulation of herpes virus-specific immunity,we studied mouse cytomegalovirus (mcmv) infection. here we demonstrate that il-10 specifically curtails the mcmv-specific cd4 t cell response by suppressing the bidirectional crosstalk between nk cells and myeloid dendritic cells (dcs). in absence of il-10,nk cells licensed dcs to effectively prime mcmv-specific cd4 t cells and we defined the pro-inflammatory cytokines il-12,ifn-γ and tnf-α as well as nk cell activating receptors nkg2d and ncr-1 to regulate this bidirectional nk/dc interplay. consequently,markedly enhanced priming of mcmv-specific cd4 t cells in il10-/- mice led to faster control of lytic viral replication,but this came at the expense of tnf-α mediated immunopathology. taken together,our data show that early induction of il-10 during mcmv infection critically regulates the strength of the innate-adaptive immune cell crosstalk,thereby impacting beneficially on the ensuing virus-host balance for both the virus and the host. © 2012 mandaric et al.