Infectious diseases are the result of interaction between pathogenic microorganisms and their host. This process is very dynamic for both the pathogen and the host and usually results in dramatic changes of gene expression in both microbial pathogen and host. During the various phases of an infection, many types of host cells including epithelial cells, endothelial cells, mesenchymal cells, cells representing innate immunity such as polymorphonuclear leukocytes, dendritic cells, and macrophages, and cells representing components of adaptive immunity such as B and T lymphocytes are involved, and some of them even directly interact with the pathogen. In consequence, these interactions result in (a) clearance of the infection by the host, or (b) an arrangement between host and pathogen in which both find their way to survive, or (c) a fatal outcome for the host. It is one of the great goals in infectious diseases to identify genes or gene products that can be used as early diagnostic markers for the different outcome of infections in order to develop individually risk-adapted treatment strategies.

In the postgenomic era a considerable number of studies on host-pathogen interactions have been published in which the gene expression response of the host or the microorganisms or even both of them have been addressed in detail. In fact, the development of novel sophisticated high-throughput technologies including transcriptomics, proteomics, and large-scale genetics led to new strategies to investigate infectious diseases. Recent data shed new light on how microbial virulence factors affect host responses, particularly immune responses. Moreover, these novel approaches allowed a more comprehensive approach to:

• identifying the specific bacterial determinants that trigger the expression of distinct sets of host genes and identifying the various signaling pathways that are involved in these gene expression programs

• identifying and investigating which features of the microbial-triggered host gene expression are common responses to diverse pathogens and which are variable and unique for certain pathogens

• dissecting how microbial virulence mechanisms which may be unique to pathogens influence and modify host responses, and unraveling how pathogens exploit host cell pathways to their own advantage in order to establish an infection

• discovering new signaling pathways and effector functions involved in host defense which are as yet unknown

In this chapter we will give an overview on how functional genomics has been used to understand the cross-talk between host and pathogen. Usually, this includes in vitro studies with various cell types and pathogens; however, few studies were done with tissues from infected patients. As many pathogens invade the host at mucosal surfaces, there are several examples of interactions with epithelial cells which will be discussed in detail. Also, many studies deal with the interaction of pathogens with cells of the innate immune system, such as macrophages and dendritic cells, as well as with pathways stimulated by pattern recognition receptors such as Toll-like receptors (TLRs).

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