Chapter 13 : Membrane Trafficking during Phagosome Formation and Maturation

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This chapter addresses the vesicular trafficking events involved in the formation and maturation of the phagosome. The reported increase in surface area during phagocytosis is most readily explained by delivery of an internal pool of membranes to the plasmalemma. Recent studies demonstrated that specific and tertiary granules contain VAMP1 and VAMP2, while azurophilic granules contain VAMP1 and VAMP7, with STX4 and SNAP23 involved in the exocytosis of these distinct populations of granules. Lysobisphosphatidic acid (LBPA) is found in late phagosomes, where it is likely to complex ALIX and direct membrane fission and the intermediate stages of maturation. Phagosome formation and maturation are impressive microbicidal tools. For this reason pathogens have developed a remarkable variety of strategies to subvert this process. Some of the most virulent and persistent bacterial pathogens such as and in fact take advantage of the phagocytic machinery to gain access into the host cell interior, where they are able to circumvent the sophisticated killing mechanism of the maturing phagosome. At present the knowledge of phagosome maturation is rudimentary and largely extrapolated from that garnered for the endocytic pathway. Some extrapolation is probably warranted, but many unique features of phagosomes will only be revealed by direct studies of particle, preferably microbial, ingestion.

Citation: Fairn G, Gershenzon E, Grinstein S. 2009. Membrane Trafficking during Phagosome Formation and Maturation, p 209-223. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch13
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Image of FIGURE 1

Schematic representation of the delivery of endomembranes to the site of phagocytosis. In addition to the area of the plasma membrane underlying the phagocytic target, several sources have been suggested to account for the membrane required to surround and engulf the particle. In neutrophils, which have highly convoluted plasma membranes, unwrinkling of folds was suggested to increase the effective area of the plasma membrane. In macrophages, early endosomes (white), late endosomes (gray), and lysosomes (black) have been suggested to fuse with the growing phagosome through SNARE-mediated fusion. A more detailed scheme of the SNARE components thought to be involved is shown in the inset. A contribution by the ER to phagosome formation has also been suggested, but this hypothesis has been questioned.

Citation: Fairn G, Gershenzon E, Grinstein S. 2009. Membrane Trafficking during Phagosome Formation and Maturation, p 209-223. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch13
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Image of FIGURE 2

Phagosome maturation. Diagram illustrating progression from a nascent phagosome through a mature phagolysosome. In the diagram maturation proceeds downward from left to right. The presence of unique markers and contributors of the maturation process is indicated. In brief, the nascent phagosome (0 min) promptly acquires Rab5, which in turn recruits p150/Vps34 to generate PI(3)P (2 to 5 min) and attracts EEA1, which facilitates tethering and fusion of early endosomes. Rab7 is then recruited (5 to 10 min), which through its binding to RILP is instrumental in promoting fusion of lysosomes with the phagosome (30 to 60 min). The late stages of maturation are characterized by the acquisition of LAMPs. Note the decrease in phagosomal pH resulting from the V-ATPase activity during the progression of the maturation sequence. See text for more details.

Citation: Fairn G, Gershenzon E, Grinstein S. 2009. Membrane Trafficking during Phagosome Formation and Maturation, p 209-223. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch13
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Image of FIGURE 3

Membrane fission during phagosome maturation. Diagram illustrating the fission events that are important in the remodeling of the phagosome during maturation. MVB formation occurs through the recruitment of Hrs, Tsg101, and the ESCRT proteins to the membrane following the ubiquitylation of cargo proteins. The cargo protein is deubiquitylated as it is diverted to the luminal vesicles of MVB. LBPA is thought to play a role in MVB formation by inducing inward budding through membrane curvature (see inset). Clathrin and COPI are two other fission complexes that contribute to outward budding during the maturation process.

Citation: Fairn G, Gershenzon E, Grinstein S. 2009. Membrane Trafficking during Phagosome Formation and Maturation, p 209-223. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch13
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Image of FIGURE 4

Potential fates of the phagosome. In the classical phagosomal maturation pathway the phagosome acquires microbicidal properties as it matures to become a phagolysosome. As pathogens are degraded a fraction of the resulting peptides (or other molecules) are transported by fission and fusion reactions to the MHC-II compartment, for antigen presentation. In some instances, phagosomes can be secreted. This is likely the case for which is extruded intact from macrophages after phagocytosis. Phagocytosis followed by exocytosis of the engulfed particle may contribute to the spread of some pathogens throughout the body of the host and may facilitate crossing of the blood-brain barrier.

Citation: Fairn G, Gershenzon E, Grinstein S. 2009. Membrane Trafficking during Phagosome Formation and Maturation, p 209-223. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch13
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