Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages
Open accessAbstract
Clearance of bacteria by macrophages involves internalization of the microorganisms into phagosomes, which are then delivered to endolysosomes for enzymatic degradation. These spatiotemporally segregated processes are not known to be functionally coupled. Here, we show that lysosomal degradation of bacteria sustains phagocytic uptake. In Drosophila and mammalian macrophages, lysosomal dysfunction due to loss of the endolysosomal Cl- transporter ClC-b/CLCN7 delayed degradation of internalized bacteria. Unexpectedly, defective lysosomal degradation of bacteria also attenuated further phagocytosis, resulting in elevated bacterial load. Exogenous application of bacterial peptidoglycans restored phagocytic uptake in the lysosomal degradation-defective mutants via a pathway requiring cytosolic pattern recognition receptors and NF-κB. Mammalian macrophages that are unable to degrade internalized bacteria also exhibit compromised NF-κB activation. Our findings reveal a role for phagolysosomal degradation in activating an evolutionarily conserved signaling cascade, which ensures that continuous uptake of bacteria is preceded by lysosomal degradation of microbes.
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Efficient degradation of phagocytic cargo sustains phagocytic uptake in macrophages.
“Efficient degradation of phagocytic cargo sustains phagocytic uptake in macrophages71,72.”
From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [72]
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INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia
Terzioglu, G., Karp, E. S., Heuer, S. E., Chadarevian, J. P., Ahsan, F. M., Haage, V. C., Davtyan, H., Fogo, G. M., Curle, A. J., Ashour, N., et al. (2025) · doi:10.1101/2025.10.27.684632 · Cited by 3 · see citing works
- Authors
- Wong, C.-O., Gregory, S., Hu, H., Chao, Y., Sepúlveda, V. E., He, Y., Li-Kroeger, D., Goldman, W. E., Bellen, H. J., & Venkatachalam, K.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of North Carolina at Chapel Hill (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wong, Ching-On
- Venkatachalam, Kartik
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 21
- Issue
- 6
- Pages
- 719-730.e6
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC5540652
- OpenAlex
- W2620909969
- Cited by
- 114
- References
- 1
- Citations by year
- 2026: 14 · 2025: 8 · 2024: 16 · 2023: 15 · 2022: 17 · 2021: 16 · 2020: 16 · 2019: 5 · 2018: 5 · 2017: 2
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P40OD018537)
- Belfer Family Foundation
- NINDS (R21NS094860, R01NS081301)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- lysosomal degradation, phagocytosis, macrophages, phagolysosomes, chloride transport, bacterial clearance, peptidoglycan, pattern recognition receptors, NF-κB activation, Drosophila, innate immunity
- MeSH terms
- RAW 264.7 Cells, Animals, Bacteria, Drosophila, Escherichia coli, Female, Humans, Immunity, Innate, Lysosomes, Macrophages, Male, Mutation, Phagocytosis, Phagosomes, Signal Transduction, Cytokines, NF-kappa B, Mice, HEK293 Cells
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