Recombinant Adenovirus Infection of Human Dendritic Cells

Recombinant Adenoviruses (rAd) are widely used as gene delivery vectors in gene therapy and vaccination (Hall et al., 2010, Liu, 2010). These replication incompetent vectors have established safety in humans and possess a number of advantages, such as that high viral titres can be produced efficiently. Several different human rAd types are being intensively investigated in clinical trials for their usefulness. In addition, there is an ever-expanding body of literature covering basic virology of Ad and interactions with host immune and other cells. It is important to understand how rAd vectors interact with specific cells of the immune system in order to improve their clinical efficacy. In particular, studies on the interaction of rAd and professional antigen presenting cells (pAPC), which specialize in recognizing pathogens and initiating a cascade of events that lead to specific immunity, are highly relevant. The most potent type of pAPC are dendritic cells (DC) that possess a unique ability to prime adaptive immune responses (Palucka & Banchereau, 1999, Palucka et al., 2010). rAd vectors likely contact DC early following inoculation and thus these cells may play a major role in regulating immunity towards the vector itself and encoded transgenes. This chapter will include a review of the current literature on the interactions between DC and rAd vectors reported by ourselves and others, in addition to a presentation of novel data. We will first summarize the phenotype and function of specific human DC subsets and methods to isolate or differentiate DC, which are crucial tools to study the interplay of DC and rAd vectors in physiologically relevant systems. Further, we will discuss basic virological aspects of rAd including vector generation and cellular receptor usage among different rAd species. While a multitude of receptors have been described for rAd, we will focus on those relevant for DC. In addition to how rAd vectors bind and infect DC, the extent by which different rAd types infect different DC subsets will be examined. Finally we will give an overview of the functional response of DC to rAd vectors, including maturation, cytokine production, and antigen presentation. Understanding how human DC sense and respond to rAd vectors will assist in guiding the use of these gene delivery vehicles in their many different clinical applications.