DOI QR코드

DOI QR Code

Mycoplasma exploits mammalian tunneling nanotubes for cell-to-cell dissemination

  • Kim, Bong-Woo (Tunneling Nanotube Research Center, Korea University) ;
  • Lee, Jae-Seon (Department of Molecular Medicine, College of Medicine, Inha University) ;
  • Ko, Young-Gyu (Tunneling Nanotube Research Center, Korea University)
  • Received : 2018.10.15
  • Accepted : 2018.11.04
  • Published : 2019.08.31

Abstract

Using tunneling nanotubes (TNTs), various pathological molecules and viruses disseminate to adjacent cells intercellularly. Here, we show that the intracellular invasion of Mycoplasma hyorhinis induces the formation of actin- and tubulin-based TNTs in various mammalian cell lines. M. hyorhinis was found in TNTs generated by M. hyorhinis infection in NIH3T3 cells. Because mycoplasma-free recipient cells received mycoplasmas from M. hyorhinis-infected donor cells in a mixed co-culture system and not a spatially separated co-culture system, direct cell-to-cell contact via TNTs was necessary for the intracellular dissemination of M. hyorhinis. The activity of Rac1, which is a small GTP binding protein, was increased by the intracellular invasion of M. hyorhinis, and its pharmacological and genetic inhibition prevented M. hyorhinis infection-induced TNT generation in NIH3T3 cells. The pharmacological and genetic inhibition of Rac1 also reduced the cell-to-cell dissemination of M. hyorhinis. Based on these data, we conclude that intracellular invasion of M. hyorhinis induces the formation of TNTs, which are used for the cell-to-cell dissemination of M. hyorhinis.

Keywords

References

  1. Stappenbeck TS and Miyoshi H (2009) The role of stromal stem cells in tissue regeneration and wound repair. Science 324, 1666-1669 https://doi.org/10.1126/science.1172687
  2. Tkach M and Thery C (2016) Communication by extracellular vesicles: Where we are and where we need to go. Cell 164, 1226-1232 https://doi.org/10.1016/j.cell.2016.01.043
  3. Schiller PC, D'Ippolito G, Brambilla R, Roos BA and Howard GA (2001) Inhibition of gap-junctional communication induces the trans-differentiation of osteoblasts to an adipocytic phenotype in vitro. J Biol Chem 276, 14133-14138 https://doi.org/10.1074/jbc.M011055200
  4. Ramirez-Weber FA and Kornberg TB (1999) Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell 97, 599-607 https://doi.org/10.1016/S0092-8674(00)80771-0
  5. Gerdes HH, Rustom A and Wang X (2013) Tunneling nanotubes, an emerging intercellular communication route in development. Mech Dev 130, 381-387 https://doi.org/10.1016/j.mod.2012.11.006
  6. Rainy N, Chetrit D, Rouger V et al (2013) H-Ras transfers from B to T cells via tunneling nanotubes. Cell Death Dis 4, e726 https://doi.org/10.1038/cddis.2013.245
  7. Rustom A, Saffrich R, Markovic I, Walther P and Gerdes HH (2004) Nanotubular highways for intercellular organelle transport. Science 303, 1007-1010 https://doi.org/10.1126/science.1093133
  8. Hurtig J, Chiu DT and Onfelt B (2010) Intercellular nanotubes: insights from imaging studies and beyond. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2, 260-276 https://doi.org/10.1002/wnan.80
  9. Abounit S, Bousset L, Loria F et al (2016) Tunneling nanotubes spread fibrillar alpha-synuclein by intercellular trafficking of lysosomes. EMBO J 35, 2120-2138 https://doi.org/10.15252/embj.201593411
  10. Gousset K, Schiff E, Langevin C et al (2009) Prions hijack tunnelling nanotubes for intercellular spread. Nat Cell Biol 11, 328-336 https://doi.org/10.1038/ncb1841
  11. Tardivel M, Begard S, Bousset L et al (2016) Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies. Acta Neuropathol Commun 4, 117 https://doi.org/10.1186/s40478-016-0386-4
  12. Kumar A, Kim JH, Ranjan P et al (2017) Influenza virus exploits tunneling nanotubes for cell-to-cell spread. Sci Rep 7, 40360 https://doi.org/10.1038/srep40360
  13. Sherer NM, Lehmann MJ, Jimenez-Soto LF, Horensavitz C, Pypaert M and Mothes W (2007) Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission. Nat Cell Biol 9, 310-315 https://doi.org/10.1038/ncb1544
  14. Panasiuk M, Rychlowski M, Derewonko N and Bienkowska-Szewczyk K (2018) Tunneling nanotubes as a novel route of cell-to-cell spread of herpesviruses. J Virol 92, e00090-18
  15. Okafo G, Prevedel L and Eugenin E (2017) Tunneling nanotubes (TNT) mediate long-range gap junctional communication: Implications for HIV cell to cell spread. Sci Rep 7, 16660 https://doi.org/10.1038/s41598-017-16600-1
  16. Onfelt B, Nedvetzki S, Benninger RK et al (2006) Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. J Immunol 177, 8476-8483 https://doi.org/10.4049/jimmunol.177.12.8476
  17. Drexler HG and Uphoff CC (2002) Mycoplasma contamination of cell cultures: Incidence, sources, effects, detection, elimination, prevention. Cytotechnology 39, 75-90 https://doi.org/10.1023/A:1022913015916
  18. Rottem S (2003) Interaction of mycoplasmas with host cells. Physiol Rev 83, 417-432 https://doi.org/10.1152/physrev.00030.2002
  19. Borovsky Z, Tarshis M, Zhang P and Rottem S (1998) Protein kinase C activation and vacuolation in HeLa cells invaded by Mycoplasma penetrans. J Med Microbiol 47, 915-922 https://doi.org/10.1099/00222615-47-10-915
  20. Winner F, Rosengarten R and Citti C (2000) In vitro cell invasion of Mycoplasma gallisepticum. Infect Immun 68, 4238-4244 https://doi.org/10.1128/IAI.68.7.4238-4244.2000
  21. Yavlovich A, Tarshis M and Rottem S (2004) Internalization and intracellular survival of Mycoplasma pneumoniae by non-phagocytic cells. FEMS Microbiol Lett 233, 241-246 https://doi.org/10.1111/j.1574-6968.2004.tb09488.x
  22. Kimura S, Hase K and Ohno H (2013) The molecular basis of induction and formation of tunneling nanotubes. Cell Tissue Res 352, 67-76 https://doi.org/10.1007/s00441-012-1518-1
  23. Arkwright PD, Luchetti F, Tour J et al (2010) Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes. Cell Res 20, 72-88 https://doi.org/10.1038/cr.2009.112
  24. Nikolic DS, Lehmann M, Felts R et al (2011) HIV-1 activates Cdc42 and induces membrane extensions in immature dendritic cells to facilitate cell-to-cell virus propagation. Blood 118, 4841-4852 https://doi.org/10.1182/blood-2010-09-305417
  25. Delage E, Cervantes DC, Penard E et al (2016) Differential identity of Filopodia and Tunneling Nanotubes revealed by the opposite functions of actin regulatory complexes. Sci Rep 6, 39632 https://doi.org/10.1038/srep39632
  26. Hanna SJ, McCoy-Simandle K, Miskolci V et al (2017) The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis. Sci Rep 7, 8547 https://doi.org/10.1038/s41598-017-08950-7
  27. Alto NM, Shao F, Lazar CS et al (2006) Identification of a bacterial type III effector family with G protein mimicry functions. Cell 124, 133-145 https://doi.org/10.1016/j.cell.2005.10.031
  28. Tran Van Nhieu G, Caron E, Hall A and Sansonetti PJ (1999) IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells. EMBO J 18, 3249-3262 https://doi.org/10.1093/emboj/18.12.3249
  29. Cardinale F, Chironna M, Chinellato I, Principi N and Esposito S (2013) Clinical relevance of Mycoplasma pneumoniae macrolide resistance in children. J Clin Microbiol 51, 723-724 https://doi.org/10.1128/JCM.02840-12