Cholesterol-Rich Membrane Rafts and Lyn Are Involved in Phagocytosis during Pseudomonas aeruginosa Infection
Abstract
The mechanism of phagocytosis of pathogens remains to be fully characterized. We report a novel phagocytosis pathway for Pseudomonas aeruginosa, which is initiated by cholesterol-rich membrane rafts and is dependent on Lyn, primarily an immune regulator with both positive and negative roles. Blocking of Lyn or blocking of cholesterol synthesis significantly inhibited phagocytosis by alveolar macrophages. We found that Lyn, via Src homology 2 and 3 domains, bound to and then activated PI3K and Akt to regulate intracellular routing of the engulfed P. aeruginosa. Further analysis indicates that Lyn and raft components entered in phagosomes and late lysosomes. Finally, respiratory burst was dependent on Lyn and membrane rafts, as confirmed by small interfering RNA and dominant-negative strategies. Our investigations demonstrate that Lyn along with membrane rafts plays a fundamental role in phagocytosis by alveolar macrophages during infection.
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Cholesterol rich membrane rafts have been shown to mediate phagocytosis of Mycobacterium, Pseudomonas or Leishmania species in macrophages.
“Cholesterol rich membrane rafts have been shown to mediate phagocytosis of Mycobacterium, Pseudomonas or Leishmania species in macrophages [41-44].”
From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [43]
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Becker, K. A., Boudreau, R. M., Gardner, A. I., Seitz, A. P., Caldwell, C. C., Li, X., Zhang, Y., Brodlie, M., Edwards, M. J., & Gulbins, E. (2018) · Springer eBooks · doi:10.1007/978-3-319-72473-7_4-1
Na, S., Hamoud, S., Aviram, M., Rom, O., Volkova, N., & Hayek, T. (2017) · doi:10.4172/2376-0354.1000209
“Moreover, cellular cholesterol has been reported to influence phagocytosis through regulation of the macrophage membrane fluidity [79].”
BackgroundThépaut, M. (2015) · doi:10.70675/8e182220zdd25z47f6z8dd9z5cd6c86ef0c6
“Des études indépendantes ont identifié que la phagocytose repose sur l’activité de la phosphoinositide 3-kinase (PI3K) dans la cellule hôte [297, 298].”
Nouveaux régulateurs de la signalisation TLR2-NF-kB
Rossi, A. (2013) · doi:10.70675/025fa282z48e2z4671zb56eze2b01383fd66
“aeruginosa par TLR2 induit, par exemple, l'endocytose du pathogène par un remaniement du cytosquelette médié par l'activation de la PI3-K via Lyn (Kannan et al., 2008).”
Goyette, G., & Desjardins, M. (2011) · doi:10.1002/9781118015759.ch10
- Authors
- Kannan, S., Audet, A., Huang, H., Chen, L.-J., & Wu, M.
- Affiliations
- University of North Dakota (US)
- State Key Laboratory for Biotherapy, West China Hospital, Sichuan University , Chengdu ,
- Sichuan University (CN)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-02
- Volume
- 180
- Issue
- 4
- Pages
- 2396-2408
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1497000882
- Cited by
- 80
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 11 · 2014: 8 · 2013: 8 · 2012: 6
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (ES014690, R03ES014690)
- National Center for Research Resources (P20RR017699)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- phagocytosis, Pseudomonas aeruginosa, Lyn kinase, alveolar macrophages, PI3K/Akt signaling, respiratory burst, phagosome maturation, bacterial infection, cholesterol biosynthesis
- MeSH terms
- Animals, Cells, Cultured, Cholesterol, Phagocytosis, Phagosomes, Pseudomonas Infections, Signal Transduction, Macrophages, Alveolar, Respiratory Burst, Rats, Sprague-Dawley, src-Family Kinases, Amino Acid Substitution, Membrane Microdomains, Mice, Rats
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