Neutral Sphingomyelinase in Physiological and Measles Virus Induced T Cell Suppression

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Though the ability of measles virus (MV) to impair T cell activation has long been known, it is mechanistically not well understood. We have shown earlier that MV can contact dependently trigger activation of sphingomyelinases which is known to affect compartmentalization of membrane lipids and proteins. Because these are particularly important in the activity of the immune synapse (IS), we investigated whether MV-induced sphingomyelinase activity would interfere at that level with T cell activation. Our study for the first time revealed that the neutral sphingomyelinase 2 (NSM2) is transiently activated in primary T cells by co-stimulation through CD3 and CD28, and that this does occur to dampen early T cell responses. The virus appears to exploit this inhibitory activity of the enzyme to suppress T cell activation by promoting an enhanced and prolonged NSM2 activation. These findings do not only assign a hitherto novel role of the NSM2 in regulating T cell responses, but also reveal a novel strategy for viral T cell suppression.

Vyšlo v časopise: Neutral Sphingomyelinase in Physiological and Measles Virus Induced T Cell Suppression. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004574
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004574

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Zdroje

1. HannunYA, ObeidLM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9: 139–150.

2. BeckerKA, GellhausA, WinterhagerE, GulbinsE (2008) Ceramide-enriched membrane domains in infectious biology and development. Subcell Biochem 49: 523–538.

3. BollingerCR, TeichgraberV, GulbinsE (2005) Ceramide-enriched membrane domains. Biochim Biophys Acta 1746: 284–294.

4. FinneganCM, RawatSS, ChoEH, GuiffreDL, LockettS, et al. (2007) Sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion. J Virol 81: 5294–5304.

5. FinneganCM, RawatSS, PuriA, WangJM, RuscettiFW, et al. (2004) Ceramide, a target for antiretroviral therapy. Proc Natl Acad Sci U S A 101: 15452–15457.

6. AvotaE, GulbinsE, Schneider-SchauliesS (2011) DC-SIGN mediated sphingomyelinase-activation and ceramide generation is essential for enhancement of viral uptake in dendritic cells. PLoS Pathog 7: e1001290.

7. de SwartRL, LudlowM, de WitteL, YanagiY, van AmerongenG, et al. (2007) Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques. PLoS Pathog 3: e178.

8. de VriesRD, McQuaidS, van AmerongenG, YukselS, VerburghRJ, et al. (2012) Measles immune suppression: lessons from the macaque model. PLoS Pathog 8: e1002885.

9. LemonK, de VriesRD, MesmanAW, McQuaidS, van AmerongenG, et al. (2011) Early target cells of measles virus after aerosol infection of non-human primates. PLoS Pathog 7: e1001263.

10. Schneider-SchauliesS, Schneider-SchauliesJ (2009) Measles virus-induced immunosuppression. Curr Top Microbiol Immunol 330: 243–269.

11. NiewieskS, EisenhuthI, FooksA, CleggJC, SchnorrJJ, et al. (1997) Measles virus-induced immune suppression in the cotton rat (Sigmodon hispidus) model depends on viral glycoproteins. J Virol 71: 7214–7219.

12. NiewieskS, OhnimusH, SchnorrJJ, GotzelmannM, Schneider-SchauliesS, et al. (1999) Measles virus-induced immunosuppression in cotton rats is associated with cell cycle retardation in uninfected lymphocytes. J Gen Virol 80 (Pt 8): 2023–2029.

13. SchlenderJ, SchnorrJJ, SpielhofferP, CathomenT, CattaneoR, et al. (1996) Interaction of measles virus glycoproteins with the surface of uninfected peripheral blood lymphocytes induces immunosuppression in vitro. Proc Natl Acad Sci U S A 93: 13194–13199.

14. ErlenhoeferC, WurzerWJ, LofflerS, Schneider-SchauliesS, ter MeulenV, et al. (2001) CD150 (SLAM) is a receptor for measles virus but is not involved in viral contact-mediated proliferation inhibition. J Virol 75: 4499–4505.

15. AvotaE, AvotsA, NiewieskS, KaneLP, BommhardtU, et al. (2001) Disruption of Akt kinase activation is important for immunosuppression induced by measles virus. Nat Med 7: 725–731.

16. AvotaE, GassertE, Schneider-SchauliesS (2010) Measles virus-induced immunosuppression: from effectors to mechanisms. Med Microbiol Immunol 199: 227–237.

17. MullerN, AvotaE, Schneider-SchauliesJ, HarmsH, KrohneG, et al. (2006) Measles virus contact with T cells impedes cytoskeletal remodeling associated with spreading, polarization, and CD3 clustering. Traffic 7: 849–858.

18. GassertE, AvotaE, HarmsH, KrohneG, GulbinsE, et al. (2009) Induction of membrane ceramides: a novel strategy to interfere with T lymphocyte cytoskeletal reorganisation in viral immunosuppression. PLoS Pathog 5: e1000623.

19. BurkhardtJK, CarrizosaE, ShafferMH (2008) The actin cytoskeleton in T cell activation. Annu Rev Immunol 26: 233–259.

20. TonnettiL, VeriMC, BonviniE, D'AdamioL (1999) A role for neutral sphingomyelinase-mediated ceramide production in T cell receptor-induced apoptosis and mitogen-activated protein kinase-mediated signal transduction. J Exp Med 189: 1581–1589.

21. BoucherLM, WiegmannK, FuttererA, PfefferK, MachleidtT, et al. (1995) CD28 signals through acidic sphingomyelinase. J Exp Med 181: 2059–2068.

22. StoffelB, BauerP, NixM, DeresK, StoffelW (1998) Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice. Eur J Immunol 28: 874–880.

23. O'ByrneD, SansomD (2000) Lack of costimulation by both sphingomyelinase and C2 ceramide in resting human T cells. Immunology 100: 225–230.

24. AbboushiN, El-HedA, El-AssaadW, KozhayaL, El-SabbanME, et al. (2004) Ceramide inhibits IL-2 production by preventing protein kinase C-dependent NF-κB activation: possible role in protein kinase Cθ regulation. J Immunol 173: 3193–3200.

25. ZechT, EjsingCS, GausK, de WetB, ShevchenkoA, et al. (2009) Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling. EMBO Journal 28: 466–476.

26. QinJ, DawsonG (2012) Evidence for coordination of lysosomal (ASMase) and plasma membrane (NSMase2) forms of sphingomyelinase from mutant mice. FEBS Lett 586: 4002–4009.

27. TaniM, HannunYA (2007) Analysis of membrane topology of neutral sphingomyelinase 2. FEBS Lett 581: 1323–1328.

28. MilhasD, ClarkeCJ, Idkowiak-BaldysJ, CanalsD, HannunYA (2010) Anterograde and retrograde transport of neutral sphingomyelinase-2 between the Golgi and the plasma membrane. Biochim Biophys Acta 1801: 1361–1374.

29. RamachandranCK, MurrayDK, NelsonDH (1990) Dexamethasone increases neutral sphingomyelinase activity and sphingosine levels in 3T3-L1 fibroblasts. Biochem Biophys Res Commun 167: 607–613.

30. GuenetJL, StanescuR, MaroteauxP, StanescuV (1981) Fragilitas ossium: a new autosomal recessive mutation in the mouse. J Hered 72: 440–441.

31. AubinI, AdamsCP, OpsahlS, SeptierD, BishopCE, et al. (2005) A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nat Genet 37: 803–805.

32. SellinCI, HorvatB (2009) Current animal models: transgenic animal models for the study of measles pathogenesis. Curr Top Microbiol Immunol 330: 111–127.

33. GrassmeH, RiethmullerJ, GulbinsE (2007) Biological aspects of ceramide-enriched membrane domains. Prog Lipid Res 46: 161–170.

34. GulbinsE, DreschersS, WilkerB, GrassmeH (2004) Ceramide, membrane rafts and infections. J Mol Med 82: 357–363.

35. ChichiliGR, WestmuckettAD, RodgersW (2010) T cell signal regulation by the actin cytoskeleton. J Biol Chem 285: 14737–14746.

36. ChurchLD, HesslerG, GoodallJE, RiderDA, WorkmanCJ, et al. (2005) TNFR1-induced sphingomyelinase activation modulates TCR signaling by impairing store-operated Ca2+ influx. J Leukoc Biol 78: 266–278.

37. Lepple-WienhuesA, BelkaC, LaunT, JekleA, WalterB, et al. (1999) Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids. Proc Natl Acad Sci U S A 96: 13795–13800.

38. HerzJ, PardoJ, KashkarH, SchrammM, KuzmenkinaE, et al. (2009) Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes. Nat Immunol 10: 761–768.

39. MittelbrunnM, Gutierrez-VazquezC, Villarroya-BeltriC, GonzalezS, Sanchez-CaboF, et al. (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2: 282.

40. TrajkovicK, HsuC, ChiantiaS, RajendranL, WenzelD, et al. (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319: 1244–1247.

41. LiJ, LiuK, LiuY, XuY, ZhangF, et al. (2013) Exosomes mediate the cell-to-cell transmission of IFN-alpha-induced antiviral activity. Nat Immunol 14: 793–803.

42. Rouquette-JazdanianAK, FoussatA, LamyL, PelassyC, LagadecP, et al. (2005) Cholera toxin B-subunit prevents activation and proliferation of human CD4+ T cells by activation of a neutral sphingomyelinase in lipid rafts. J Immunol 175: 5637–5648.

43. QinJ, BerdyshevE, PoirerC, SchwartzNB, DawsonG (2012) Neutral sphingomyelinase 2 deficiency increases hyaluronan synthesis by up-regulation of Hyaluronan synthase 2 through decreased ceramide production and activation of Akt. J Biol Chem 287: 13620–13632.

44. BabichA, LiS, O'ConnorRS, MiloneMC, FreedmanBD, et al. (2012) F-actin polymerization and retrograde flow drive sustained PLCγ1 signaling during T cell activation. J Cell Biol 197: 775–787.

45. GormanJA, BabichA, DickCJ, SchoonRA, KoenigA, et al. (2012) The Cytoskeletal Adaptor Protein IQGAP1 Regulates TCR-Mediated Signaling and Filamentous Actin Dynamics. J Immunol 188: 6135–6144.

46. AbeM, MakinoA, Hullin-MatsudaF, KamijoK, Ohno-IwashitaY, et al. (2012) A role for sphingomyelin-rich lipid domains in the accumulation of phosphatidylinositol-4, 5-bisphosphate to the cleavage furrow during cytokinesis. Mol Cell Biol 32: 1396–1407.

47. IkenouchiJ, HirataM, YonemuraS, UmedaM (2013) Sphingomyelin clustering is essential for the formation of microvilli. J Cell Sci 126: 3585–3592.

48. TaniM, HannunYA (2007) Neutral sphingomyelinase 2 is palmitoylated on multiple cysteine residues. Role of palmitoylation in subcellular localization. J Biol Chem 282: 10047–10056.

49. TellierE, Negre-SalvayreA, BocquetB, ItoharaS, HannunYA, et al. (2007) Role for furin in tumor necrosis factor α-induced activation of the matrix metalloproteinase/sphingolipid mitogenic pathway. Mol Cell Biol 27: 2997–3007.