A role for the phagosome in cytokine secretion.
Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. We found a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Tumor necrosis factor alpha (TNFalpha) is trafficked from the Golgi to the recycling endosome (RE), where vesicle-associated membrane protein 3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNFalpha and expands the membrane for phagocytosis.
Murray
Rachael Z
RZ
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
Kay
Jason G
JG
Sangermani
Daniele G
DG
Stow
Jennifer L
JL
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis; D010588:Phagosomes / Q000502:physiology*; D050765:Qa-SNARE Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D051040:Vesicle-Associated Membrane Protein 3 / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis; D000099193:rab11 GTP-Binding Proteins
D007371:Interferon-gamma; D050765:Qa-SNARE Proteins; D014409:Tumor Necrosis Factor-alpha; D051040:Vesicle-Associated Membrane Protein 3; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C494953:vesicle-associated membrane protein 3, mouse