MyD88-dependent silencing of transgene expression during the innate and adaptive immune response to helper-dependent adenovirus.

ABSTRACT: Activation of the host innate immune response after systemic administration of adenoviral vectors constitutes a principal impediment to successful clinical gene replacement therapies. Although helper-dependent adenoviruses (HDAds) lack all viral functional genes, systemic administration of a high dose of HDAd still elicits a potent innate immune response in host animals. Toll-like receptors (TLRs) are innate receptors that sense microbial products and trigger the maturation of antigen-presenting cells and cytokine production via MyD88-dependent signaling (except TLR3). Here we show that mice lacking MyD88 exhibit a dramatic reduction in proinflammatory cytokines after intravenous injection of a high dose of HDAd, and show significantly reduced induction of the adaptive immune response when

SUBMITTER: Suzuki M 

PROVIDER: S-EPMC2865218 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature