Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling

SOLMAZ, GÜLHAS; GOHMERT, MELANIE; JACOBS, ROLAND; BORKNER, LISA; WAGNER, HERMANN; FRANCOZO, MARCELA; LINDENBERG, MARC; TUFA, DEJENE; KÜHL, ANJA A.; HOLZMANN, BERNARD; SPARWASSER, TIM; PUTTUR, FRANZ; BUENO, CARLOS; SWALLOW, MAXINE; LIENENKLAUS, STEFAN; CICIN-SAIN, LUKA; BEROD, LUCIANA

Cell Reports

Elsevier B.V.

Año: 2016 vol. 17 p. 1113 - 1127

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.