A role for the phagosome in cytokine secretion
Abstract
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 α (TNFα) 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 TNFα and expands the membrane for phagocytosis.
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In macrophages, TNF is released to the extracellular milieu via the constitutive secretion pathway, and its trafficking is the best understood of all cytokines.
“In macrophages, TNF is released to the extracellular milieu via the constitutive secretion pathway, and its trafficking is the best understood of all cytokines (9, 17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [17]
LPS increases the expression of vesicle trafficking proteins that regulate TNF trafficking.
“Moreover, LPS was found to increase the expression of vesicle trafficking proteins that regulate TNF trafficking (17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [17]
The Stx4/SNAP23/VAMP3 complex facilitates the passage of TNF from recycling endosomes to the cell membrane.
“Thence, the Stx4/SNAP23/VAMP3 complex facilitates the passage of TNF from recycling endosomes to the cell membrane (17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [17]
After synthesis in the ER, the SNARE proteins Stx6, Stx7, Vtib mediate the fusion of TNF-containing vesicles from the Golgi complex with VAMP3+-recycling endosomes.
“After synthesis in the ER, the SNARE proteins Stx6, Stx7, Vtib mediate the fusion of TNF-containing vesicles from the Golgi complex with VAMP3+-recycling endosomes (17, 19).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [17]
TNF is secreted not only to the extracellular milieu at the plasma membrane, but also in a polarized manner at the phagocytic cup.
“Interestingly, it was found that TNF is not only secreted to the extracellular milieu at the plasma membrane, but also in a polarized manner at the phagocytic cup (17).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [17]
The post-Golgi trafficking of IL-6 follows a route that is dependent on Stx6 and Vti1b, which form a complex with cognate SNARE VAMP3 at recycling endosomes.
“The post-Golgi trafficking of IL-6 follows a route that is also dependent on Stx6 and Vti1b, which form a complex with cognate SNARE VAMP3 at recycling endosomes (17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [17]
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References 20 · Cited by 330
- Authors
- Murray, R. Z., Kay, J. G., Sangermani, D. G., & Stow, J. L.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Stow, Jennifer L.
- Venue
- Science
- Published
- 2005-12-02
- Volume
- 310
- Issue
- 5753
- Pages
- 1492-1495
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1587819404
- Cited by
- 330
- References
- 20
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 10 · 2023: 11 · 2022: 14 · 2021: 20 · 2020: 10 · 2019: 12 · 2018: 14 · 2017: 19 · 2016: 21 · 2015: 15 · 2014: 11 · 2013: 24 · 2012: 20
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Faculty of Health; Institute of Health and Biomedical Innovation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- phagosome, cytokine production, TNF-α, macrophages, membrane trafficking, recycling endosomes, phagocytosis, Golgi apparatus, phagocytic cup, innate immunity
- MeSH terms
- rab11 GTP-Binding Proteins, Animals, Candida albicans, Cell Line, Cell Membrane, Interferon-gamma, Macrophage Activation, Macrophages, Phagocytosis, Phagosomes, Endosomes, Tumor Necrosis Factor-alpha, rab GTP-Binding Proteins, Cytoplasmic Vesicles, Qa-SNARE Proteins, Vesicle-Associated Membrane Protein 3, Mice
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