Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of
The fungus Candida albicans is not only a commensal of the digestive system, but also a common cause of human opportunistic infections. Macrophages and dendritic cells can eliminate C. albicans by phagocytosis, a complex process that involves extensive membrane reorganization at the cell surface. The extent to which membrane lipids, including sphingolipids, contribute to the proper execution of phagocytosis remains largely unknown. Pharmacological blockade of sphingolipid biosynthesis by the small molecule inhibitors myriocin and fumonisin B1 impairs phagocytosis of C. albicans. DC2.4 dendritic cells genetically deficient in Sptlc2, the enzyme that catalyzes the first and rate-limiting step in the sphingolipid biosynthetic pathway, are likewise defective in phagocytosis of C. albicans. Sptlc2-/- DC2.4 cells showed reduced binding of C. albicans, but overall membrane transport and protein secretion remained functional. Sptlc2-deficient cells express reduced levels of the receptors Dectin-1 and TLR2 at the cell surface, and are unable to form a normal phagocytic cup. Exogenous addition of the major ganglioside GM1 restored phagocytic ability of Sptlc2-/- DC2.4 cells. Mice with compromised sphingolipid production upon in vivo treatment with fumonisin B1 fail to eradicate C. albicans, consistent with the in vitro results. Sphingolipids are thus essential for clearance of fungal infection through phagocytosis, and hence indispensable for the proper functioning of the innate immune system.
Vyšlo v časopise:
Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005188
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1005188
Souhrn
The fungus Candida albicans is not only a commensal of the digestive system, but also a common cause of human opportunistic infections. Macrophages and dendritic cells can eliminate C. albicans by phagocytosis, a complex process that involves extensive membrane reorganization at the cell surface. The extent to which membrane lipids, including sphingolipids, contribute to the proper execution of phagocytosis remains largely unknown. Pharmacological blockade of sphingolipid biosynthesis by the small molecule inhibitors myriocin and fumonisin B1 impairs phagocytosis of C. albicans. DC2.4 dendritic cells genetically deficient in Sptlc2, the enzyme that catalyzes the first and rate-limiting step in the sphingolipid biosynthetic pathway, are likewise defective in phagocytosis of C. albicans. Sptlc2-/- DC2.4 cells showed reduced binding of C. albicans, but overall membrane transport and protein secretion remained functional. Sptlc2-deficient cells express reduced levels of the receptors Dectin-1 and TLR2 at the cell surface, and are unable to form a normal phagocytic cup. Exogenous addition of the major ganglioside GM1 restored phagocytic ability of Sptlc2-/- DC2.4 cells. Mice with compromised sphingolipid production upon in vivo treatment with fumonisin B1 fail to eradicate C. albicans, consistent with the in vitro results. Sphingolipids are thus essential for clearance of fungal infection through phagocytosis, and hence indispensable for the proper functioning of the innate immune system.
Zdroje
1. Janeway C.A. Jr. and Medzhitov R., Innate immune recognition. Annu Rev Immunol, 2002. 20: p. 197–216. 11861602
2. Yeung T. and Grinstein S., Lipid signaling and the modulation of surface charge during phagocytosis. Immunol Rev, 2007. 219: p. 17–36. 17850479
3. Underhill D.M. and Goodridge H.S., Information processing during phagocytosis. Nat Rev Immunol, 2012. 12(7): p. 492–502. doi: 10.1038/nri3244 22699831
4. Swanson J.A., Shaping cups into phagosomes and macropinosomes. Nat Rev Mol Cell Biol, 2008. 9(8): p. 639–49. doi: 10.1038/nrm2447 18612320
5. Gonnord P., Blouin C.M., and Lamaze C., Membrane trafficking and signaling: two sides of the same coin. Semin Cell Dev Biol, 2012. 23(2): p. 154–64. doi: 10.1016/j.semcdb.2011.11.002 22085846
6. Xu S., et al., Activated dectin-1 localizes to lipid raft microdomains for signaling and activation of phagocytosis and cytokine production in dendritic cells. J Biol Chem, 2009. 284(33): p. 22005–11. doi: 10.1074/jbc.M109.009076 19525229
7. Kwiatkowska K., Frey J., and Sobota A., Phosphorylation of FcgammaRIIA is required for the receptor-induced actin rearrangement and capping: the role of membrane rafts. J Cell Sci, 2003. 116(Pt 3): p. 537–50. 12508114
8. Strzelecka-Kiliszek A., et al., Activated FcgammaRII and signalling molecules revealed in rafts by ultra-structural observations of plasma-membrane sheets. Mol Membr Biol, 2004. 21(2): p. 101–8. 15204439
9. Botelho R.J., et al., Localized biphasic changes in phosphatidylinositol-4,5-bisphosphate at sites of phagocytosis. J Cell Biol, 2000. 151(7): p. 1353–68. 11134066
10. Beemiller P., Hoppe A.D., and Swanson J.A., A phosphatidylinositol-3-kinase-dependent signal transition regulates ARF1 and ARF6 during Fcgamma receptor-mediated phagocytosis. PLoS Biol, 2006. 4(6): p. e162. 16669702
11. Marshall J.G., et al., Restricted accumulation of phosphatidylinositol 3-kinase products in a plasmalemmal subdomain during Fc gamma receptor-mediated phagocytosis. J Cell Biol, 2001. 153(7): p. 1369–80. 11425868
12. Kamen L.A., Levinsohn J., and Swanson J.A., Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes. Mol Biol Cell, 2007. 18(7): p. 2463–72. 17442886
13. Coppolino M.G., et al., Inhibition of phosphatidylinositol-4-phosphate 5-kinase Ialpha impairs localized actin remodeling and suppresses phagocytosis. J Biol Chem, 2002. 277(46): p. 43849–57. 12223494
14. Henry R.M., et al., The uniformity of phagosome maturation in macrophages. J Cell Biol, 2004. 164(2): p. 185–94. 14718518
15. Holthuis J.C. and Levine T.P., Lipid traffic: floppy drives and a superhighway. Nat Rev Mol Cell Biol, 2005. 6(3): p. 209–20. 15738987
16. van Meer G., Voelker D.R., and Feigenson G.W., Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol, 2008. 9(2): p. 112–24. doi: 10.1038/nrm2330 18216768
17. Manes S., del Real G., and Martinez A.C., Pathogens: raft hijackers. Nat Rev Immunol, 2003. 3(7): p. 557–68. 12876558
18. Kwik J., et al., Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin. Proc Natl Acad Sci U S A, 2003. 100(24): p. 13964–9. 14612561
19. Pizzo P., et al., Lipid rafts and T cell receptor signaling: a critical re-evaluation. Eur J Immunol, 2002. 32(11): p. 3082–91. 12385028
20. Hinkovska-Galcheva V., et al., Enhanced phagocytosis through inhibition of de novo ceramide synthesis. J Biol Chem, 2003. 278(2): p. 974–82. 12424251
21. Magenau A., et al., Phagocytosis of IgG-coated polystyrene beads by macrophages induces and requires high membrane order. Traffic, 2011. 12(12): p. 1730–43. doi: 10.1111/j.1600-0854.2011.01272.x 21883764
22. Maceyka M. and Spiegel S., Sphingolipid metabolites in inflammatory disease. Nature, 2014. 510(7503): p. 58–67. doi: 10.1038/nature13475 24899305
23. Tafesse F.G., Ternes P., and Holthuis J.C., The multigenic sphingomyelin synthase family. J Biol Chem, 2006. 281(40): p. 29421–5. 16905542
24. Hojjati M.R., Li Z., and Jiang X.C., Serine palmitoyl-CoA transferase (SPT) deficiency and sphingolipid levels in mice. Biochim Biophys Acta, 2005. 1737(1): p. 44–51. 16216550
25. Hanada K., et al., Sphingolipids are essential for the growth of Chinese hamster ovary cells. Restoration of the growth of a mutant defective in sphingoid base biosynthesis by exogenous sphingolipids. J Biol Chem, 1992. 267(33): p. 23527–33. 1429697
26. Miyake Y., et al., Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin. Biochem Biophys Res Commun, 1995. 211(2): p. 396–403. 7794249
27. He Q., et al., Ceramide synthase inhibition by fumonisin B1 treatment activates sphingolipid-metabolizing systems in mouse liver. Toxicol Sci, 2006. 94(2): p. 388–97. 16960033
28. Tafesse F.G., et al., Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins. Proc Natl Acad Sci U S A, 2013. 110(16): p. 6406–11. doi: 10.1073/pnas.1219909110 23576732
29. Rodriguez-Boulan E., Kreitzer G., and Musch A., Organization of vesicular trafficking in epithelia. Nat Rev Mol Cell Biol, 2005. 6(3): p. 233–47. 15738988
30. Delgado A., et al., Inhibitors of sphingolipid metabolism enzymes. Biochim Biophys Acta, 2006. 1758(12): p. 1957–77. 17049336
31. Hanada K., Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta, 2003. 1632(1–3): p. 16–30. 12782147
32. Wang E., et al., Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. J Biol Chem, 1991. 266(22): p. 14486–90. 1860857
33. Tafesse F.G., et al., Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells. J Biol Chem, 2007. 282(24): p. 17537–47. 17449912
34. Kitatani K., Idkowiak-Baldys J., and Hannun Y.A., The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell Signal, 2008. 20(6): p. 1010–8. doi: 10.1016/j.cellsig.2007.12.006 18191382
35. Hannun Y.A. and Obeid L.M., Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol, 2008. 9(2): p. 139–50. doi: 10.1038/nrm2329 18216770
36. Goodridge H.S., Simmons R.M., and Underhill D.M., Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J Immunol, 2007. 178(5): p. 3107–15. 17312158
37. Rogers N.C., et al., Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity, 2005. 22(4): p. 507–17. 15845454
38. Steinshamn S. and Waage A., Tumor necrosis factor and interleukin-6 in Candida albicans infection in normal and granulocytopenic mice. Infect Immun, 1992. 60(10): p. 4003–8. 1398912
39. Hojjati M.R., et al., Effect of myriocin on plasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice. J Biol Chem, 2005. 280(11): p. 10284–9. 15590644
40. Fujita T., et al., Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot (Tokyo), 1994. 47(2): p. 208–15.
41. Mukhopadhyay K., et al., Membrane sphingolipid-ergosterol interactions are important determinants of multidrug resistance in Candida albicans. Antimicrob Agents Chemother, 2004. 48(5): p. 1778–87. 15105135
42. Flannagan R.S., Jaumouille V., and Grinstein S., The cell biology of phagocytosis. Annu Rev Pathol, 2012. 7: p. 61–98. doi: 10.1146/annurev-pathol-011811-132445 21910624
43. Flannagan R.S., et al., Dynamic macrophage "probing" is required for the efficient capture of phagocytic targets. J Cell Biol, 2010. 191(6): p. 1205–18. doi: 10.1083/jcb.201007056 21135140
44. Riedl J., et al., Lifeact: a versatile marker to visualize F-actin. Nat Methods, 2008. 5(7): p. 605–7. doi: 10.1038/nmeth.1220 18536722
45. Plato A., Hardison S.E., and Brown G.D., Pattern recognition receptors in antifungal immunity. Semin Immunopathol, 2015. 37(2): p. 97–106. doi: 10.1007/s00281-014-0462-4 25420452
46. Drummond R.A., et al., Innate Defense against Fungal Pathogens. Cold Spring Harb Perspect Med, 2014.
47. Zhang Y.J., et al., Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing. Cell, 2013. 155(6): p. 1296–308. doi: 10.1016/j.cell.2013.10.045 24315099
48. Schmidt F.I., et al., Vaccinia virus entry is followed by core activation and proteasome-mediated release of the immunomodulatory effector VH1 from lateral bodies. Cell Rep, 2013. 4(3): p. 464–76. doi: 10.1016/j.celrep.2013.06.028 23891003
49. Mercer J. and Helenius A., Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells. Science, 2008. 320(5875): p. 531–5. doi: 10.1126/science.1155164 18436786
50. Matlin K.S., et al., Pathway of vesicular stomatitis virus entry leading to infection. J Mol Biol, 1982. 156(3): p. 609–31. 6288961
51. Lingwood D. and Simons K., Lipid rafts as a membrane-organizing principle. Science, 2010. 327(5961): p. 46–50. doi: 10.1126/science.1174621 20044567
52. Obeid L.M., et al., Programmed cell death induced by ceramide. Science, 1993. 259(5102): p. 1769–71. 8456305
53. Wymann M.P. and Schneiter R., Lipid signalling in disease. Nat Rev Mol Cell Biol, 2008. 9(2): p. 162–76. doi: 10.1038/nrm2335 18216772
54. Diaz-Rohrer B.B., et al., Membrane raft association is a determinant of plasma membrane localization. Proc Natl Acad Sci U S A, 2014. 111(23): p. 8500–5. doi: 10.1073/pnas.1404582111 24912166
55. Hauck C.R., et al., Acid sphingomyelinase is involved in CEACAM receptor-mediated phagocytosis of Neisseria gonorrhoeae. FEBS Lett, 2000. 478(3): p. 260–6. 10930579
56. Aderem A. and Underhill D.M., Mechanisms of phagocytosis in macrophages. Annu Rev Immunol, 1999. 17: p. 593–623. 10358769
57. Levin R., Grinstein S., and Schlam D., Phosphoinositides in phagocytosis and macropinocytosis. Biochim Biophys Acta, 2014.
58. Bohdanowicz M. and Grinstein S., Role of phospholipids in endocytosis, phagocytosis, and macropinocytosis. Physiol Rev, 2013. 93(1): p. 69–106. doi: 10.1152/physrev.00002.2012 23303906
59. Duran J.M., et al., Sphingomyelin organization is required for vesicle biogenesis at the Golgi complex. EMBO J, 2012. 31(24): p. 4535–46. doi: 10.1038/emboj.2012.317 23178595
60. Sharpe H.J., Stevens T.J., and Munro S., A comprehensive comparison of transmembrane domains reveals organelle-specific properties. Cell, 2010. 142(1): p. 158–69. doi: 10.1016/j.cell.2010.05.037 20603021
61. Mouritsen O.G., Model answers to lipid membrane questions. Cold Spring Harb Perspect Biol, 2011. 3(9): p. a004622. doi: 10.1101/cshperspect.a004622 21610116
62. Goodridge H.S., et al., Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. Nature, 2011. 472(7344): p. 471–5. doi: 10.1038/nature10071 21525931
63. Goodridge H.S., Underhill D.M., and Touret N., Mechanisms of Fc receptor and dectin-1 activation for phagocytosis. Traffic, 2012. 13(8): p. 1062–71. doi: 10.1111/j.1600-0854.2012.01382.x 22624959
64. Trajkovic K., et al., Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 2008. 319(5867): p. 1244–7. doi: 10.1126/science.1153124 18309083
65. Hurley J.H., et al., Membrane budding. Cell, 2010. 143(6): p. 875–87. doi: 10.1016/j.cell.2010.11.030 21145455
66. Ewers H., et al., GM1 structure determines SV40-induced membrane invagination and infection. Nat Cell Biol, 2010. 12(1): p. 11–8; sup pp 1–12. doi: 10.1038/ncb1999 20023649
67. Romer W., et al., Actin dynamics drive membrane reorganization and scission in clathrin-independent endocytosis. Cell, 2010. 140(4): p. 540–53. doi: 10.1016/j.cell.2010.01.010 20178746
68. Tam C., et al., Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. J Cell Biol, 2010. 189(6): p. 1027–38. doi: 10.1083/jcb.201003053 20530211
69. Mercer J. and Helenius A., Virus entry by macropinocytosis. Nat Cell Biol, 2009. 11(5): p. 510–20. doi: 10.1038/ncb0509-510 19404330
70. Swanson J.A. and Watts C., Macropinocytosis. Trends Cell Biol, 1995. 5(11): p. 424–8. 14732047
71. Ahmed S.N., Brown D.A., and London E., On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes: physiological concentrations of cholesterol and sphingolipid induce formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes. Biochemistry, 1997. 36(36): p. 10944–53. 9283086
72. Simons K. and Ikonen E., Functional rafts in cell membranes. Nature, 1997. 387(6633): p. 569–72. 9177342
73. Simons K. and Sampaio J.L., Membrane organization and lipid rafts. Cold Spring Harb Perspect Biol, 2011. 3(10): p. a004697. doi: 10.1101/cshperspect.a004697 21628426
74. Munro S., Lipid rafts: elusive or illusive? Cell, 2003. 115(4): p. 377–88. 14622593
75. Strijbis K., et al., Bruton's Tyrosine Kinase (BTK) and Vav1 contribute to Dectin1-dependent phagocytosis of Candida albicans in macrophages. PLoS Pathog, 2013. 9(6): p. e1003446. doi: 10.1371/journal.ppat.1003446 23825946
76. Li X., et al., The beta-glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance. Cell Host Microbe, 2011. 10(6): p. 603–15. doi: 10.1016/j.chom.2011.10.009 22177564
77. Guo B., et al., Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex. Immunity, 2000. 13(2): p. 243–53. 10981967
78. Moffatt M.F., et al., Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature, 2007. 448(7152): p. 470–3. 17611496
79. Breslow D.K., et al., Orm family proteins mediate sphingolipid homeostasis. Nature, 2010. 463(7284): p. 1048–53. doi: 10.1038/nature08787 20182505
80. Dawkins J.L., et al., Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet, 2001. 27(3): p. 309–12. 11242114
81. Schulze H. and Sandhoff K., Lysosomal lipid storage diseases. Cold Spring Harb Perspect Biol, 2011. 3(6).
82. Mali P., et al., RNA-guided human genome engineering via Cas9. Science, 2013. 339(6121): p. 823–6. doi: 10.1126/science.1232033 23287722
83. Tafesse F.G., et al., GPR107, a G-protein-coupled Receptor Essential for Intoxication by Pseudomonas aeruginosa Exotoxin A, Localizes to the Golgi and Is Cleaved by Furin. J Biol Chem, 2014. 289(35): p. 24005–18. doi: 10.1074/jbc.M114.589275 25031321
84. Bligh E.G. and Dyer W.J., A rapid method of total lipid extraction and purification. Can J Biochem Physiol, 1959. 37(8): p. 911–7. 13671378
85. Folch J., Lees M., and Sloane Stanley G.H., A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem, 1957. 226(1): p. 497–509. 13428781
86. Hu C., et al., RPLC-ion-trap-FTMS method for lipid profiling of plasma: method validation and application to p53 mutant mouse model. J Proteome Res, 2008. 7(11): p. 4982–91. doi: 10.1021/pr800373m 18841877
87. Bird S.S., et al., Serum lipidomics profiling using LC-MS and high-energy collisional dissociation fragmentation: focus on triglyceride detection and characterization. Anal Chem, 2011. 83(17): p. 6648–57. doi: 10.1021/ac201195d 21774539
88. Yamada T., et al., Development of a lipid profiling system using reverse-phase liquid chromatography coupled to high-resolution mass spectrometry with rapid polarity switching and an automated lipid identification software. J Chromatogr A, 2013. 1292: p. 211–8. doi: 10.1016/j.chroma.2013.01.078 23411146
89. Taguchi R. and Ishikawa M., Precise and global identification of phospholipid molecular species by an Orbitrap mass spectrometer and automated search engine Lipid Search. J Chromatogr A, 2010. 1217(25): p. 4229–39. doi: 10.1016/j.chroma.2010.04.034 20452604
90. Smith M.H., et al., The preparation and characterization of anti-peptide heteroantisera recognizing subregions of the intracytoplasmic domain of class I H-2 antigens. Mol Immunol, 1986. 23(10): p. 1077–92. 3796619
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 10
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Chronobiomics: The Biological Clock as a New Principle in Host–Microbial Interactions
- Interferon-γ: The Jekyll and Hyde of Malaria
- Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins
- Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes