Plasticity of Dendritic Cell Transcriptional Responses to Antigen: Functional States of Dendritic Cells

The vertebrate immune system protects the host from harmful encounters with pathogenic microorganisms and other dangerous components of the environment. To do this the immune system must gather information about the ‘nonself’ pathogens and by processing this information, initiate an appropriate immunological response. The immune system represents an example of emergent behavior from a complex, multifactorial, adaptive system. To understand emergent behavior we need to know the systems components and the rules that govern the system. To identify the components, immunology research has catalogued and characterized probably all major cell types involved in the innate and adaptive immune response. In the postgenomic world, we are now able to further characterize global changes in cellular gene expression and thereby identify and infer changes in the functional state of the cells. Together this should allow modeling of immune system function. Dendritic cells orchestrate the host immune response. By identifying a pathogen and processing this information through a coordinated differentiation program, phenotypic changes effected in dentritic cells allow appropriate information to be conveyed to the adaptive arm of the immune system, thereby shaping downstream immunological responses. Transcriptional profiling of human and mouse dendritic cell responses to different antigens have demonstrated this functional plasticity. Understanding the regulation of these dendritic cell differentiation states will contribute to computational models of the immune system, and our understanding of the parameters that affect the immune system response to infection.