From Grazing to Host Defense

Phagocytosis is an ancient and evolutionary highly conserved process by which cells engulf particles. Protozoa use phagocytosis primarily to obtain nutrients. In metazoa, with a developed immune system, phagocytosis is a feature of specialized, "professional phagocytes" such as macrophages, neutrophils and dendritic cells, which are capable of ingesting and killing a large variety of microorganisms [1]. In the light of evolution, protozoa and nonvertebrates may be viewed as an "ancient virulence school" for microbes which later developed into human pathogens. In the course of this coevolution, numerous bacterial species developed defense mechanisms against phagocytic cells, including the production of large filaments, antiphagocytic capsules or the secretion of toxins [2, 3]. Some pathogens even evolved strategies to reprogram their host cells, thereby ensuring intracellular survival or replication.

A better understanding of the cross-talk between phagocytic host cells and microbes was catalyzed by the observation that so-called model organisms can be infected by certain pathogens. In fact, it has been shown that many of the virulence factors required for pathogenicity in mammals are also important for pathogen survival during interactions with unicellular organisms and nonvertebrate hosts [4]. Because of their lower level of complexity, host models such as Dictyostelium discoideum and Drosophila melanogaster often allow a better dissection of the innate immune system, undisturbed by superimposed effects of the acquired immune system [5]. The organisms are easy to cultivate and, more importantly amenable to genetic manipulation, which facilitates identification and analysis of genes regulating phagocytosis and modulating host resistance to pathogens. Recent genome projects have also offered a variety of new target genes for testing expression patterns during infection. In the this chapter we will focus on phagocytosis and the outcome of ingestion of pathogens in the D. discoideum and the D. melanogaster model.

66 | 4 Cellular Model Systems Used to Study Phagosome Biogenesis 4.2

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