%0 Journal Article %1 Puttur20161113 %A Puttur, F %A Francozo, M %A Solmaz, G %A Bueno, C %A Lindenberg, M %A Gohmert, M %A Swallow, M %A Tufa, D %A Jacobs, R %A Lienenklaus, S %A Kühl, A A %A Borkner, L %A Cicin-Sain, L %A Holzmann, B %A Wagner, H %A Berod, L %A Sparwasser, T %D 2016 %J Cell Reports %K sparwasser %N 4 %P 1113 - 1127 %T Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via \TLR9\ and MyD88 Signaling %V 17 %X Summary Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse \CMV\ (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c+ dendritic cells (DCs) strongly enhances \MCMV\ clearance by boosting natural killer (NK) cell \CD69\ expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid \DCs\ (pDCs), conventional \DCs\ (cDCs) promote robust \NK\ cell effector function and \MCMV\ clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates \NK\ cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of \TLR9\ and MyD88 signaling in individual \DC\ subsets and evaluate the mechanism by which cDCs control \MCMV\ immunity.

@article{Puttur20161113, abstract = {Summary Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse \{CMV\} (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c+ dendritic cells (DCs) strongly enhances \{MCMV\} clearance by boosting natural killer (NK) cell \{CD69\} expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid \{DCs\} (pDCs), conventional \{DCs\} (cDCs) promote robust \{NK\} cell effector function and \{MCMV\} clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates \{NK\} cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of \{TLR9\} and MyD88 signaling in individual \{DC\} subsets and evaluate the mechanism by which cDCs control \{MCMV\} immunity. }, added-at = {2016-11-03T18:21:33.000+0100}, author = {Puttur, F and Francozo, M and Solmaz, G and Bueno, C and Lindenberg, M and Gohmert, M and Swallow, M and Tufa, D and Jacobs, R and Lienenklaus, S and Kühl, A A and Borkner, L and Cicin-Sain, L and Holzmann, B and Wagner, H and Berod, L and Sparwasser, T}, biburl = {https://www.bibsonomy.org/bibtex/2aa9bfddbd099947bd856eae728c1b42d/sparwasser}, interhash = {cbe18885bb0eabe8335ec937a86a2559}, intrahash = {aa9bfddbd099947bd856eae728c1b42d}, journal = {Cell Reports }, keywords = {sparwasser}, number = 4, pages = {1113 - 1127}, pubmedurl = {https://www.ncbi.nlm.nih.gov/pubmed/27760315}, timestamp = {2016-11-03T18:21:33.000+0100}, title = {Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via \{TLR9\} and MyD88 Signaling }, volume = 17, year = 2016 }