Fcγ receptors and toll-like receptor 9 synergize to drive immune complex-induced dendritic cell maturation

Previous in vivo studies established that inactivated Francisella tularensis immune complexes (mAb-iFt) are a more protective vaccine against lethal tularemia than iFt alone. Subsequent in vitro studies revealed enhanced DC maturation marker expression with mAb-iFt stimulation. The goal of this study was to determine the mechanism of enhanced DC maturation. Multiparameter analysis of surface marker expression and cytokine secretion demonstrates a requirement for FcγR signaling in enhanced DC maturation. MyD88 was also found to be essential for heightened DC maturation, implicating MyD88-dependent TLRs in DC maturation. Upon further study, we discovered that TLRs 2 & 4 drive cytokine secretion, but surprisingly TLR9 is required for DC maturation marker upregulation. These studies reveal a separation of DC cytokine and maturation marker induction pathways and demonstrate that FcγR-TLR/MyD88 synergy underlies the enhanced dendritic cell maturation in response to the mAb-iFt vaccine.