Skip to main content

Advertisement

SpringerLink
Log in

Enteric glial cells are susceptible to Clostridium difficile toxin B

  • Original Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Clostridium difficile causes nosocomial/antibiotic-associated diarrhoea and pseudomembranous colitis. The major virulence factors are toxin A and toxin B (TcdB), which inactivate GTPases by monoglucosylation, leading to cytopathic (cytoskeleton alteration, cell rounding) and cytotoxic effects (cell-cycle arrest, apoptosis). C. difficile toxins breaching the intestinal epithelial barrier can act on underlying cells, enterocytes, colonocytes, and enteric neurons, as described in vitro and in vivo, but until now no data have been available on enteric glial cell (EGC) susceptibility. EGCs are crucial for regulating the enteric nervous system, gut homeostasis, the immune and inflammatory responses, and digestive and extradigestive diseases. Therefore, we evaluated the effects of C. difficile TcdB in EGCs. Rat-transformed EGCs were treated with TcdB at 0.1–10 ng/ml for 1.5–48 h, and several parameters were analysed. TcdB induces the following in EGCs: (1) early cell rounding with Rac1 glucosylation; (2) early G2/M cell-cycle arrest by cyclin B1/Cdc2 complex inactivation caused by p27 upregulation, the downregulation of cyclin B1 and Cdc2 phosphorylated at Thr161 and Tyr15; and (3) apoptosis by a caspase-dependent but mitochondria-independent pathway. Most importantly, the stimulation of EGCs with TNF-α plus IFN-γ before, concomitantly or after TcdB treatment strongly increased TcdB-induced apoptosis. Furthermore, EGCs that survived the cytotoxic effect of TcdB did not recover completely and showed not only persistent Rac1 glucosylation, cell-cycle arrest and low apoptosis but also increased production of glial cell-derived neurotrophic factor, suggesting self-rescuing mechanisms. In conclusion, the high susceptibility of EGCs to TcdB in vitro, the increased sensitivity to inflammatory cytokines related to apoptosis and the persistence of altered functions in surviving cells suggest an important in vivo role of EGCs in the pathogenesis of C. difficile infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16

Similar content being viewed by others

Abbreviations

TcdA:

Toxin A of Clostridium difficile

TcdB:

Toxin B of Clostridium difficile

EGCs:

Enteric glial cells

ENS:

Enteric nervous system

GDNF:

Glial cell-derived neurotrophic factor

NGF:

Nerve growth factor

TNF-α:

Tumour necrosis factor-alpha

IFN-γ:

Interferon-gamma

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Foetal bovine serum

PI:

Propidium iodide

IL-1β :

Interleukin-1beta 

U:

Densitometric units

CDKs:

Cyclin-dependent kinases

Cdc2:

Cell division cycle 2

GFAP:

Glial fibrillary acidic protein

PARP:

Poly (ADP-ribose) polymerase

BAF:

Boc-Asp(OMe)-fluoromethylketone

Z-DEVD-FMK:

Z-Asp-Glu-Val-Asp-fluoromethylketone

ROCK1:

Rho-associated coiled-coil containing kinase 1

PAK1:

p21-activated kinase 1

PI3K:

Phosphatidylinositide 3-kinase

JNK:

c-Jun N-terminal kinase

References

  1. Cloud J, Kelly CP (2007) Update on Clostridium difficile associated disease. Curr Opin Gastroenterol 23:4–9

    PubMed  Google Scholar 

  2. Pothoulakis C, Lamont JT (2001) Microbes and microbial toxins: paradigms for microbial-mucosal interactions II. The integrated response of the intestine to Clostridium difficile toxins. Am J Physiol Gastrointest Liver Physiol 280:G178–G183

    CAS  PubMed  Google Scholar 

  3. Lyerly DM, Krivan HC, Wilkins TD (1988) Clostridium difficile: its disease and toxins. Clin Microbiol Rev 1:1–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sun X, Savidge T, Feng H (2010) The enterotoxicity of Clostridium difficile toxins. Toxins (Basel) 2:1848–1880

    Article  CAS  Google Scholar 

  5. Pruitt RN, Lacy DB (2012) Toward a structural understanding of Clostridium difficile toxins A and B. Front Cell Infect Microbiol 2:1–28

    Article  Google Scholar 

  6. Voth DE, Ballard JD (2005) Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 18:247–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lyras D, O’Connor JR, Howarth PM, Sambol SP, Carter GP, Phumoonna T, Poon R, Adams V, Vedantam G, Johnson S, Gerding DN, Rood JI (2009) Toxin B is essential for virulence of Clostridium difficile. Nature 458:1176–1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Aktories K, Just I (2005) Clostridial Rho-inhibiting protein toxins. Curr Top Microbiol Immunol 291:113–145

    CAS  PubMed  Google Scholar 

  9. Huelsenbeck J, Dreger S, Gerhard R, Barth H, Just I, Genth H (2007) Difference in the cytotoxic effects of toxin B from Clostridium difficile strain VPI 10463 and Toxin B from variant Clostridium difficile strain 1470. Infect Immun 75:801–809

    Article  CAS  PubMed  Google Scholar 

  10. Genth H, Huelsenbeck J, Hartmann B, Hofmann F, Just I, Gerhard R (2006) Cellular stability of Rho-GTPases glucosylated by Clostridium difficile toxin B. FEBS Lett 580:3565–3569

    Article  CAS  PubMed  Google Scholar 

  11. Halabi-Cabezon I, Huelsenbeck J, May M, Ladwein M, Rottner K, Just I, Genth H (2008) Prevention of the cytopathic effect induced by Clostridium difficile toxin B by active Rac1. FEBS Lett 582:3751–3756

    Article  CAS  PubMed  Google Scholar 

  12. Popoff MR, Geny B (2011) Rho/Ras-GTPase-dependent and -independent activity of clostridial glucosylating toxins. J Med Microbiol 60:1057–1069

    Article  CAS  PubMed  Google Scholar 

  13. Bishop AL, Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348:241–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420:629–635

    Article  CAS  PubMed  Google Scholar 

  15. Karlsson R, Pedersen ED, Wang Z, Brakebusch C (2009) Rho GTPase function in tumorigenesis. Biochim Biophys Acta 1796:91–98

    CAS  PubMed  Google Scholar 

  16. Fiorentini C, Arancia G, Paradisi S, Donelli G, Giuliano M, Piemonte F, Mastrantonio P (1989) Effects of Clostridium difficile Toxins A and B on cytoskeleton organization in HEp-2 cells: a comparative morphological study. Toxicon 27:1209–1218

    Article  CAS  PubMed  Google Scholar 

  17. Riegler M, Sedivy R, Pothoulakis C, Hamilton G, Zacherl J, Bischof G, Cosentini E, Feil W, Schiessel R, LaMont JT, Wenzi E (1995) Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest 95:2004–2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gerhard R, Nottrott S, Schoentaube J, Tatge H, Olling A, Just I (2008) Glucosylation of Rho GTPases by Clostridium difficile toxin A triggers apoptosis in intestinal epithelial cells. J Med Microbiol 57:765–770

    Article  CAS  PubMed  Google Scholar 

  19. Fiorentini C, Fabbri A, Falzano L, Fattorossi A, Matarrese P, Rivabene R, Donelli G (1998) Clostridium difficile toxin B induces apoptosis in intestinal cultured cells. Infect Immun 66:2660–2665

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Brito GA, Fujji J, Carneiro-Filho BA, Lima AA, Obrig T, Guerrant RL (2002) Mechanism of Clostridium difficile toxin A-induced apoptosis in T84 cells. J Infect Dis 186:1438–1447

    Article  CAS  PubMed  Google Scholar 

  21. Mahida YR, Galvin A, Makh S, Hyde S, Sanfilippo L, Borriello SP, Sewell HF (1998) Effect of Clostridium difficile toxin A on human colonic lamina propria cells: early loss of macrophages followed by T-cell apoptosis. Infect Immun 66:5462–5469

    CAS  PubMed  PubMed Central  Google Scholar 

  22. He D, Hagen SJ, Pothoulakis C, Chen M, Medina ND, Warny M, LaMont JT (2000) Clostridium difficile toxin A causes early damage to mitochondria in cultured cells. Gastroenterology 119:139–150

    Article  CAS  PubMed  Google Scholar 

  23. Linseman D, Laessig T, Meintzer MK, McClure M, Barth H, Aktories K, Heidenreich KA (2001) An essential role for Rac/Cdc42 GTPases in cerebellar granule neuron survival. J Biol Chem 276:39123–39131

    Article  CAS  PubMed  Google Scholar 

  24. Hippenstiel S, Schmeck B, N’Guessan PD, Seybold J, Krull M, Preissner K, Eichel-Streiber CV, Suttorp N (2002) Rho protein inactivation induced apoptosis of cultured human endothelial cells. Am J Physiol Lung Cell Mol Physiol 283:L830–L838

    Article  CAS  PubMed  Google Scholar 

  25. Kim H, Kokkotou E, Na X, Rhee SH, Moyer MP, Pothoulakis C, Lamont JT (2005) Clostridium difficile toxin A-induced colonocyte apoptosis involves p53-dependent p21(WAF1/CIP1) induction via p38 mitogen-activated protein kinase. Gastroenterology 129:1875–1888

    Article  CAS  PubMed  Google Scholar 

  26. Matarrese P, Falzano L, Fabbri A, Gambardella L, Frank C, Geny B, Popoff MR, Malorni W, Fiorentini C (2007) Clostridium difficile toxin B causes apoptosis in epithelial cells by thrilling mitochondria. Involvement of ATP-sensitive mitochondrial potassium channels. J Biol Chem 282:9029–9041

    Article  CAS  PubMed  Google Scholar 

  27. Nottrott S, Schoentaube J, Genth H, Just I, Gerhard R (2007) Clostridium difficile toxin A-induced apoptosis is p53-independent but depends on glucosylation of Rho GTPases. Apoptosis 12:1443–1453

    Article  CAS  PubMed  Google Scholar 

  28. Qa’Dan M, Ramsey M, Daniel J, Spyres LM, Safiejko-Mroczka B, Ortiz-Leduc W, Ballard JD (2002) Clostridium difficile toxin B activates dual caspase-dependent and caspase-independent apoptosis in intoxicated cells. Cell Microbiol 4:425–434

    Article  PubMed  Google Scholar 

  29. Savidge TC, Pan WH, Newman P, O’Brien M, Anton PM, Pothoulakis C (2003) Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine. Gastroenterology 125:413–420

    Article  CAS  PubMed  Google Scholar 

  30. Yu YB, Li YQ (2014) Enteric glial cells and their role in the intestinal epithelial barrier. World J Gastroenterol 20:11273–11280

    Article  PubMed  PubMed Central  Google Scholar 

  31. Neunlist M, Rolli-Derkinderen M, Latorre R, Van Landeghem L, Coron E, Derkinderen P, De Giorgio R (2014) Enteric glial cells: recent developments and future directions. Gastroenterology 147:1230–1237

    Article  CAS  PubMed  Google Scholar 

  32. Gulbransen BD (2014) Enteric glia. Colloquium series on neuroglia in biology and medicine: from physiology to disease. Morgan & Claypool Publishers, San Rafael, pp 1–70

    Google Scholar 

  33. Gulbransen BD, Sharkey KA (2012) Novel functional roles for enteric glia in the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 9:625–632

    Article  CAS  PubMed  Google Scholar 

  34. Cirillo C, Sarnelli G, Esposito G, Turco F, Steardo L, Cuomo R (2011) S100B protein in the gut: the evidence for enteroglial-sustained intestinal inflammation. World J Gastroenterol 17:1261–1266

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bassotti G, Villanacci V, Maurer CA, Fisogni S, Di Fabio F, Cadei M, Morelli A, Panagiotis T, Cathomas G, Salerni B (2006) The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation. Gut 55:41–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bassotti G, Villanacci V (2011) Can “functional” constipation be considered as a form of enteric neuro-gliopathy? Glia 59:345–350

    Article  PubMed  Google Scholar 

  37. Rühl A, Trotter J, Stremmel W (2001) Isolation of enteric glia and establishment of transformed enteroglial cell lines from the myenteric plexus of adult rat. Neurogastroenterol Motil 13:95–106

    Article  PubMed  Google Scholar 

  38. Soret R, Coquenlorge S, Cossais F, Meurette G, Rolli-Derkinderen M, Neunlist M (2013) Characterization of human, mouse, and rat cultures of enteric glial cells and their effect on intestinal epithelial cells. Neurogastroenterol Motil 25:e755–e764

    Article  CAS  PubMed  Google Scholar 

  39. Fettucciari K, Rosati E, Scaringi L, Cornacchione P, Migliorati G, Sabatini R, Fetriconi I, Rossi R, Marconi P (2000) Group B Streptococcus induces apoptosis in macrophages. J Immunol 165:3923–3933

    Article  CAS  PubMed  Google Scholar 

  40. Fettucciari K, Fetriconi I, Mannucci R, Nicoletti I, Bartoli A, Coaccioli S, Marconi P (2006) Group B Streptococcus induces macrophage apoptosis by calpain activation. J Immunol 176:7542–7556

    Article  CAS  PubMed  Google Scholar 

  41. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) J Immunol Methods 139:271–279

    Article  CAS  PubMed  Google Scholar 

  42. Gerashchenko BI, Azzam EI, Howell RW (2004) Cytometry A 61:134–141

    Article  PubMed  Google Scholar 

  43. von Boyen GBT (2004) Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia. Gut 53:222–228

    Article  Google Scholar 

  44. May M, Wang T, Müller M, Genth H (2013) Difference in F-actin depolymerization induced by toxin B from the Clostridium difficile strain VPI 10463 and toxin B from the variant Clostridium difficile serotype F strain 1470. Toxins (Basel) 5:106–119

    Article  CAS  Google Scholar 

  45. Vermeulen K, Berneman ZN, Van Bockstaele DR (2003) Cell-cycle and apoptosis. Cell Prolif 36:165–175

    Article  CAS  PubMed  Google Scholar 

  46. Jacotot E, Ferri KF, Kroemer G (2000) Apoptosis and cell cycle: distinct checkpoints with overlapping upstream control. Pathol Biol (Paris) 48:271–279

    CAS  Google Scholar 

  47. Su CC, Lin JG, Chen GW, Lin WC, Chung JG (2006) Down-regulation of Cdc25c, CDK1 and cyclin B1 and up-regulation of Wee1 by curcumin promotes human colon cancer colo 205 cell entry into G2/M-phase of cell cycle. Cancer Genom Proteom 3:55–62

    CAS  Google Scholar 

  48. Zhang XH, Zou ZQ, Xu CW, Shen YZ, Li D (2011) Myricetin induces G2/M phase arrest in HepG2 cells by inhibiting the activity of the cyclin B/Cdc2 complex. Mol Med Rep 4:273–277

    CAS  PubMed  Google Scholar 

  49. Ando Y, Yasuda S, Oceguera-Yanez F, Narumiya S (2007) Inactivation of Rho GTPases with Clostridium difficile toxin B impairs centrosomal activation of Aurora-A in G2/M transition of HeLa cells. Mol Biol Cell 18:3752–3763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Malumbres M, Barbacid M (2005) Mammalian cyclin-dependent kinases. Trends Biochem Sci 30:630–641

    Article  CAS  PubMed  Google Scholar 

  51. Wyllie AH (2010) “Where, O death, is thy sting?” A brief review of apoptosis biology. Mol Neurobiol 42:4–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kaufmann SH, Hengartner MO (2001) Programmed cell death: alive and well in the new millennium. Trends Cell Biol 11:526–534

    Article  CAS  PubMed  Google Scholar 

  53. Street CA, Bryan BA (2011) Rho kinase proteins—pleiotropic modulators of cell survival and apoptosis. Anticancer Res 31:3645–3657

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Schoentaube J, Olling A, Tatge H, Just I, Gerhard R (2009) Serine-71 phosphorylation of Rac1/Cdc42 diminishes the pathogenic effect of Clostridium difficile toxin A. Cell Microbiol 11:1816–1826

    Article  CAS  PubMed  Google Scholar 

  55. Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y (2004) Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 101:7618–7623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Yoshida T, Zhang Y, Rivera Rosado LA, Chen J, Khan T, Moon SY, Zhang B (2010) Blockade of Rac1 activity induces G1 cell cycle arrest or apoptosis in breast cancer cells through downregulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein. Mol Cancer Ther 9:1657–1668

    Article  CAS  PubMed  Google Scholar 

  57. Stankiewicz TR, Ramaswami SA, Bouchard RJ, Aktories K, Linseman DA (2015) Neuronal apoptosis induced by selective inhibition of Rac GTPase versus global suppression of Rho family GTPases is mediated by alterations in distinct mitogen-activated protein kinase signaling cascades. J Biol Chem 290:9363–9376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Steele J, Chen K, Sun X, Zhang Y, Wang H, Tzipori S, Feng H (2012) Systemic dissemination of Clostridium difficile toxins A and B is associated with severe, fatal disease in animal models. J Infect Dis 205:384–391

    Article  CAS  PubMed  Google Scholar 

  59. Czepiel J, Biesiada G, Brzozowski T, Ptak-Belowska A, Perucki W, Birczynska M, Jurczyszyn A, Strzalka M, Targosz A, Garlicki A (2014) The role of local and systemic cytokines in patients infected with Clostridium difficile. J Physiol Pharmacol 65:695–703

    CAS  PubMed  Google Scholar 

  60. Steinkamp M, Schulte N, Spaniol U, Pflüger C, Hartmann C, Kirsch J, von Boyen GB (2012) Brain derived neurotrophic factor inhibits apoptosis in enteric glia during gut inflammation. Med Sci Monit 18:BR117–BR122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Steinkamp M, Gundel H, Schulte N, Spaniol U, Pflueger C, Zizer E, von Boyen GB (2012) GDNF protects enteric glia from apoptosis: evidence for an autocrine loop. BMC Gastroenterol 12:1–6

    Article  Google Scholar 

  62. Shi J, Wei L (2007) Rho kinase in the regulation of cell death and survival. Arch Immunol Ther Exp (Warsz) 55:61–75

    Article  Google Scholar 

  63. Coqueret O (2003) New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol 13:65–70

    Article  CAS  PubMed  Google Scholar 

  64. Katayose Y, Kim M, Rakkar AN, Li Z, Cowan KH, Seth P (1997) Promoting apoptosis: a novel activity associated with the cyclin-dependent kinase inhibitor p27. Cancer Res 57:5441–5445

    CAS  PubMed  Google Scholar 

  65. Wang X, Gorospe M, Huang Y, Holbrook NJ (1997) p27Kip1 overexpression causes apoptotic death of mammalian cells. Oncogene 15:2991–2997

    Article  CAS  PubMed  Google Scholar 

  66. Kim HJ, Ghil KC, Kim MS, Yeo SH, Chun YJ, Kim MY (2005) Potentiation of ceramide-induced apoptosis by p27kip1 overexpression. Arch Pharm Res 28:87–92

    Article  CAS  PubMed  Google Scholar 

  67. Besson A, Dowdy SF, Roberts JM (2008) CDK inhibitors: cell cycle regulators and beyond. Dev Cell 14:159–169

    Article  CAS  PubMed  Google Scholar 

  68. Airaksinen MS, Saarma M (2002) The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 3:383–394

    Article  CAS  PubMed  Google Scholar 

  69. Xiao W, Wang W, Chen W, Sun L, Li X, Zhang C, Yang H (2014) GDNF is involved in the barrier-inducing effect of enteric glial cells on intestinal epithelial cells under acute ischemia reperfusion stimulation. Mol Neurobiol 50:274–289

    Article  CAS  PubMed  Google Scholar 

  70. Sariola H, Saarma M (2003) Novel functions and signalling pathways for GDNF. J Cell Sci 116:3855–3862

    Article  CAS  PubMed  Google Scholar 

  71. De Giorgio R, Giancola F, Boschetti E, Abdo H, Lardeux B, Neunlist M (2012) Enteric glia and neuroprotection: basic and clinical aspects. Am J Physiol Gastrointest Liver Physiol 303:G887–G893

    Article  PubMed  Google Scholar 

  72. Ochoa-Cortes F, Turco F, Linan-Rico A, Soghomonyan S, Whitaker E, Wehner S, Cuomo R, Christofi FL (2016) Enteric glial cells: a new frontier in neurogastroenterology and clinical target for inflammatory Bowel diseases. Inflamm Bowel Dis 22:433–449

    Article  PubMed  Google Scholar 

  73. Sethi S, Garey KW, Arora V, Ghantoji S, Rowan P, Smolensky M, DuPont HL (2011) Increased rate of irritable bowel syndrome and functional gastrointestinal disorders after Clostridium difficile infection. J Hosp Infect 77:172–173

    Article  CAS  PubMed  Google Scholar 

  74. Piche T, Vanbiervliet G, Pipau FG, Dainese R, Hébuterne X, Rampal P, Collins SM (2007) Low risk of irritable bowel syndrome after Clostridium difficile infection. Can J Gastroenterol 21:727–731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wadhwa A, Al Nahhas MF, Dierkhising RA, Patel R, Kashyap P, Pardi DS, Khanna S, Grover M (2016) High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection. Aliment Pharmacol Ther 44:576–582

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Springer Nature Author Services for editing of English language. We are greatly indebted to Alfa Wasserman, Sofar, and Almirall companies for their generous unrestricted support. This work was supported by a Project from the Department of Experimental Medicine for Basic Research (bando 2014) awarded to Doctor Katia Fettucciari, a Grant from Fondazione Cassa di Risparmio di Perugia, Italy (bando 2015-2015.0327.021 Ricerca Scientifica e Tecnologica) to Professor Lanfranco Corazzi, and a grant from “AIGO fa RICERCA” awarded to Professor Gabrio Bassotti by the Italian Society of Hospital Gastroenterologists and Endoscopists (AIGO).

Author information

Authors and Affiliations

  1. Department of Experimental Medicine, Histology and Medical Embryology Section, Perugia University, Piazza Lucio Severi 1, Edificio B IV piano, Sant’Andrea delle Fratte, 06132, Perugia, Italy

    Katia Fettucciari, Pamela Ponsini, Davide Gioè & Pierfrancesco Marconi

  2. Department of Medicine, Gastroenterology, Hepatology and Digestive Endoscopy Section, Perugia University, Perugia, Italy

    Gabrio Bassotti

  3. Department of Experimental Medicine, Physiology and Biochemistry Section, Perugia University, Perugia, Italy

    Lara Macchioni & Lanfranco Corazzi

  4. Department of Clinical Sciences and Translational Medicine, Tor Vergata University, Rome, Italy

    Camilla Palumbo

  5. Gastroenterology Section, Perugia General Hospital, Perugia, Italy

    Elisabetta Antonelli

  6. Department of Medicine, Internal Medicine, Rheumatology and Medical Therapy of Pain Section, Perugia University, District of Terni, Perugia, Italy

    Stefano Coaccioli

  7. Pathology Section, Spedali Civili, Brescia, Italy

    Vincenzo Villanacci

Authors
  1. Katia Fettucciari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pamela Ponsini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Davide Gioè
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lara Macchioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Camilla Palumbo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elisabetta Antonelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stefano Coaccioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vincenzo Villanacci
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lanfranco Corazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pierfrancesco Marconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gabrio Bassotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katia Fettucciari.

Ethics declarations

Conflict of interest

The authors declare no financial or commercial conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (TIFF 15168 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fettucciari, K., Ponsini, P., Gioè, D. et al. Enteric glial cells are susceptible to Clostridium difficile toxin B. Cell. Mol. Life Sci. 74, 1527–1551 (2017). https://doi.org/10.1007/s00018-016-2426-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-016-2426-4

Keywords

Search

Navigation