Because so many DC properties are affected by acti-United Kingdom vation, it is hard to come up with an all-encompassing definition of the term. Adding to the difficulty, it is not Introduction clear that all forms of DC activation necessarily result A stable environment and an abundant supply of nutriin increased immunogenicity. For example, some forms ents make an inviting place for a pathogen. Conse- of activation could selectively increase delivery of signal quently, complex multicellular organisms have had to 1 without signal 2, giving rise to tolerogenic rather than evolve defense mechanisms to make their internal envi- immunogenic DC (see Manickasingham and Reis e ronment more hostile to invaders. All immune systems Sousa, 2001, for a discussion). Here, activation is used have one feature in common: they respond to infection simply to refer to a change from the resting state. This by switching from a resting to an active state. For exam- can refer to any changes that affect the ability of APC ple, Drosophila flies do not make microbicidal peptides to deliver signals 1, 2, and/or 3 to T cells, including until infected by fungi or bacteria. Similarly, T and B changes in expression of surface markers, cytokine procells are generally resting in the absence of infection duction, migratory properties, endocytic activity, moralthough they can be rapidly activated in response to phology, or longevity. This broad definition allows for an invading pathogen. Thus, there must be key features the possibility that there may be multiple forms of DC of an infectious process that trigger immune responses. activation with different functional consequences. These features are recognized primarily by cells and DC activation is generally seen in response to pathomolecules of the innate immune system. The innate re- gens or hallmarks of their presence. For example, live sponse limits infection and activates antigen-presenting infection or injection of rodents with LPS, extracts of cells (APC) to trigger adaptive immunity, which in- microorganisms, double-stranded RNA (dsRNA), or baccreases specificity and generates memory. Over the last terial DNA can all trigger changes in DC expression of 25 years, dendritic cells (DC) have emerged as the major MHC, adhesion and costimulatory molecules, and in APC involved in this process. DC provide T cells with cytokine production. Similarly, resting DC grown in vitro antigens as complexes with MHC or MHC-like molecules from mouse or human progenitors can be rapidly actiand, simultaneously, deliver critical information about vated by exposure to lipopolysaccharide (LPS), inflamthe context in which the antigens were encountered. An matory cytokines, dsRNA, heat-shock proteins (HSPs), infectious context promotes DC immunogenicity and or other stimuli. DC activation in this context is thought the development of immunity while absence of infection to lead to increased immunogenicity and may be seen fails to do so. DC also convey information about the as a physiological response to infection with profound nature of the infectious agent, favoring the appropriate implications for T cell immunity. class of T cell response. This review explores the topic Direct Activation of DC by PAMPs of DC as sensors of infection and its consequences for How does infection trigger DC activation? Janeway prothe adaptive response. posed that APC possess germline-encoded pattern rec-Dendritic Cell Activation ognition receptors (PRRs) that recognize and are triggered by evolutionarily conserved molecules essential DC comprise a large family of leukocytes with related to pathogen function, which are absent from the host morphology and the potential to …