| First Author | Mandaric S | Year | 2012 |
| Journal | PLoS Pathog | Volume | 8 |
| Issue | 8 | Pages | e1002846 |
| PubMed ID | 22876184 | Mgi Jnum | J:195373 |
| Mgi Id | MGI:5478681 | Doi | 10.1371/journal.ppat.1002846 |
| Citation | Mandaric S, et al. (2012) IL-10 suppression of NK/DC crosstalk leads to poor priming of MCMV-specific CD4 T cells and prolonged MCMV persistence. PLoS Pathog 8(8):e1002846 |
| abstractText | 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-gamma and TNF-alpha 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-alpha 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. |
