Introduction

Phagocytosis is an evolutionarily ancient process that is believed to have evolved around the dawn of eukaryotic cell history to enable amoeboid cells to take up bacteria, which still provide a food source for the modern free-living amoeboid cells. In higher eukaryotes, this process is predominantly the function of three specialized "professional" phagocytes: macrophages, neutrophils and dendritic cells. The process of phagocytosis has been extensively covered by many excellent reviews [1-8]. Figure 8.1 summarizes the main stages involved in the life of a "permissive" latex bead phagosome (LBP) undergoing the full program of "maturation" [9]. This term describes how phagosomes fuse sequentially with different intracellular organelles, culminating in the end-stage, the phagolysosome. In parallel, lipids and proteins are lost from phagosomes by recycling of vesicles [10]. As seen in Figure 8.1, this process is accompanied by a progressive lowering of the organelle pH, under the control of the proton ATPase [11].

There are three major filament systems in eukaryotic cells, comprising actin, microtubules (MTs) and intermediate filaments (IFs). Since a role of IFs in phagocytosis has not been described, we will focus here on the actin and MT systems. Together, these two filament systems are important for the phagocytic uptake process, for recycling from the phagosome and for phagosome intracellular transport and fusion with endocytic organelles.

Here, we will address the interactions of the actin and MT systems with assembled phagosomes. Since most of the studies on these interactions have been carried out using the latex bead phagosome macrophage model system, most of our discussion will be centered on that system. We will not focus in detail on the role of the cytoskeleton in the phagocytic uptake process, a topic that has been extensively covered in a number of good reviews [12-14]. The ability of different pathogens to alter different aspects of phagosome maturation, including the cytoskeleton, has also been a major interest in the field. Many comprehensive reviews are available that cover most aspects of the cytoskeleton-pathogen interaction [12-19].

Figure 8.1 Scheme of phagosome maturation. Latex beads coated with ligands are recognized by receptors at the plasma membrane (1). Then the bead is taken up by pseudopodia generated in an actin-dependent way; membrane is provided by intracellular vesicles from different sources (2). After closure (3) the bead is located in phagosomes that follow a process of maturation fusing with components of the endocytic pathway (4A) or recycling its content (4B). The whole process is accompanied by a progressive acidification of the phagosome. This process of maturation is dependent on microtubules and actin. EE, early endosome; LE/Lys, late endosome-lysosome; Lys, lysosome.

Figure 8.1 Scheme of phagosome maturation. Latex beads coated with ligands are recognized by receptors at the plasma membrane (1). Then the bead is taken up by pseudopodia generated in an actin-dependent way; membrane is provided by intracellular vesicles from different sources (2). After closure (3) the bead is located in phagosomes that follow a process of maturation fusing with components of the endocytic pathway (4A) or recycling its content (4B). The whole process is accompanied by a progressive acidification of the phagosome. This process of maturation is dependent on microtubules and actin. EE, early endosome; LE/Lys, late endosome-lysosome; Lys, lysosome.

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