- Email: [email protected]
Trypanosome invasion of mammalian cells requires activation of the TGF-β signaling pathway
Comment immunological explanations for the patterns cannot yet be ruled out. It should be possible to test more of the models’ predictions with the data emerging from this very significant study.
3 4 5 6
References I Butterworth. A.E. (1994) Porasltoiogy Today IO, 378-380 2 Gtyseels, B. (1994) Parasitology Today IO.
7 8
380-384 Gryseels, B. et a/ ( 1994) Trap. Geogr. Med, 46, 209-219 Chandlwana, S.K. et al. (199 I) Parasltoiogy IO2,73-83 Anderson, R.M. and May, R M. (I 985) Nature 3 IS. 493 -496 Woolhouse. M.E.J. ( 1994) Parasitology Today IO, 196-202 Woolhouse, M.E J ( 1994) Parasite Immunoi. /6,4 I S-424 Woolhouse, M.E.J. ei a/ (I 994) Trans. R. Sot.
Trypanorome Invasion of Mammalian Cells Requires Activation of the TGF-P Signaling Pathway M. Ming, M.E. Ewen and M.E.A. Pererra Cell 82, 287-296 The adherence of tr-ypomastlgotes to the outer membrane of host cells (a prelude to intracellular invasion) is mediated by at least two parasite ligand reactions with carbohydrate receptor epitopes on the host cell surface: transsialidase (which reacts with c&3-linked sialyi epitopes) and penetrin (which reacts with heparan sulfate moietres). Binding does not guarantee access of the parasite to the host cell cytoplasm, which would seem to require activation of specific signaling pathways. This would be analogous to cellular invasion by viruses and bactena, which activates surface membrane signaling molecules. The purpose of the research resulting in the publication of this paper IS
the search for the nature of these signaling pathways. To this end, Pereira and colleagues measured Try~onosomo cruzl invasion of cell lines that were either activated with growth factors or resistant to cytoklne strmulatron. They report that ttypomastigotes attached to epithelral cells that lack transforming growth factor B (TGF-B) receptor I or II but could neither Invade nor replicate. Both invasion and TGF-B activation were restored by transfection with TGF-P receptor genes, and in a hybrid of TGF-B-t-esistant bladder and colon carcinoma cells. Cells that had had their intracellular slgnalrng cascade impaired by either constitutive expression of the cyclindependent krnase gene cdk4 or the
Trap.Med. Hyg. 88, 520-526 9 Woolhouse, M.E.J. (1992) Parasite lmmunoi. 14.563-578
Note: See Letters, this issue. Mark Zoology,
Woo/house is at the Deportment of Unlven,ty of Oxford, South Pork
Road, Oxford, UK OXI 3PS.Tel: +44 1865 27 1244, Fax: +44 1865 310447, e-mail: [email protected]
oncogene H-ras were resistant to T. cruzi invasion, but this was reversed following treatment with TGF-B. Finally, infective ttypomastigotes induced a TGF-P-responsive reporter gene in TGF-P-sensitive but not in TGF-Pinsensitive cell lines. Non-infective trypomastigotes did not have this effect. TGF-B induces signaling that leads to a range of biological activities (eg. regulation of cell proliferation and differentiation, modulation of inflammatory responses). The conclusion of this research is that T. cruzi subverts the TGF-P signaling system to further its own end: access to the host cell n cytoplasm.
Outlook was compiled by T. Saklatvala.
Fondazione Ivo de Carneri ‘Forthe
promotion of control strategies against parasitic diseases in developing countries and to encourage
research in parasitology’
Professor Ivo de Carneri ( I927- 1993) was one of the great European parasitologists. Some will remember him as a laboratory scientist at NIMR (London, UK), The Carlo Erba Institute (Milan, Spain) and The Schiffs und Tropen Institute (Hamburg, Germany), while others will remember the enthusiasm he brought to field studies involving topics as diverse as cutaneous leishmaniasis in the Mato Gross0 and helminthiasis in Zanzibar. Perhaps his most lasting contribution, however, was as an educator; many young scientists acquired their first interest in parasitology through his teaching as Professor, and later as Chair of Parasitology at the University of Pavia, and through the courses in tropical medicine he initiated in developing countries. His classic book, Parassitologia General e Umona, is now in its I Ith edition - possibly a unique achievement for a university text in parasitology. The Fondazione Ivo de Carneri was established in October 1994; its objectives and activities include: l to promote research and training in parasite disease control through the construction of a public health laboratory in Pemba Island, Zanzibar, United Republic of Tanzania; l to encourage the study of parasitology by sustaining the revision and re-publication of Pcmssitologia General e Umana under the auspices of a Scientific Editorial Committee; l to support the development of young researchers from sub-Saharan Africa through the award of the Ivo de Carneri Prize for doctoral theses in parasitology. For more information on the Foundation, or to make a contribution towards its activities, please contact: Fondazione Ivo de Carneri, Via G Ceradini 3, 20 I29 Milano, Italy. Tel/Fax: +39 2738 1695.
3 4 5 6
References I Butterworth. A.E. (1994) Porasltoiogy Today IO, 378-380 2 Gtyseels, B. (1994) Parasitology Today IO.
7 8
380-384 Gryseels, B. et a/ ( 1994) Trap. Geogr. Med, 46, 209-219 Chandlwana, S.K. et al. (199 I) Parasltoiogy IO2,73-83 Anderson, R.M. and May, R M. (I 985) Nature 3 IS. 493 -496 Woolhouse. M.E.J. ( 1994) Parasitology Today IO, 196-202 Woolhouse, M.E J ( 1994) Parasite Immunoi. /6,4 I S-424 Woolhouse, M.E.J. ei a/ (I 994) Trans. R. Sot.
Trypanorome Invasion of Mammalian Cells Requires Activation of the TGF-P Signaling Pathway M. Ming, M.E. Ewen and M.E.A. Pererra Cell 82, 287-296 The adherence of tr-ypomastlgotes to the outer membrane of host cells (a prelude to intracellular invasion) is mediated by at least two parasite ligand reactions with carbohydrate receptor epitopes on the host cell surface: transsialidase (which reacts with c&3-linked sialyi epitopes) and penetrin (which reacts with heparan sulfate moietres). Binding does not guarantee access of the parasite to the host cell cytoplasm, which would seem to require activation of specific signaling pathways. This would be analogous to cellular invasion by viruses and bactena, which activates surface membrane signaling molecules. The purpose of the research resulting in the publication of this paper IS
the search for the nature of these signaling pathways. To this end, Pereira and colleagues measured Try~onosomo cruzl invasion of cell lines that were either activated with growth factors or resistant to cytoklne strmulatron. They report that ttypomastigotes attached to epithelral cells that lack transforming growth factor B (TGF-B) receptor I or II but could neither Invade nor replicate. Both invasion and TGF-B activation were restored by transfection with TGF-P receptor genes, and in a hybrid of TGF-B-t-esistant bladder and colon carcinoma cells. Cells that had had their intracellular slgnalrng cascade impaired by either constitutive expression of the cyclindependent krnase gene cdk4 or the
Trap.Med. Hyg. 88, 520-526 9 Woolhouse, M.E.J. (1992) Parasite lmmunoi. 14.563-578
Note: See Letters, this issue. Mark Zoology,
Woo/house is at the Deportment of Unlven,ty of Oxford, South Pork
Road, Oxford, UK OXI 3PS.Tel: +44 1865 27 1244, Fax: +44 1865 310447, e-mail: [email protected]
oncogene H-ras were resistant to T. cruzi invasion, but this was reversed following treatment with TGF-B. Finally, infective ttypomastigotes induced a TGF-P-responsive reporter gene in TGF-P-sensitive but not in TGF-Pinsensitive cell lines. Non-infective trypomastigotes did not have this effect. TGF-B induces signaling that leads to a range of biological activities (eg. regulation of cell proliferation and differentiation, modulation of inflammatory responses). The conclusion of this research is that T. cruzi subverts the TGF-P signaling system to further its own end: access to the host cell n cytoplasm.
Outlook was compiled by T. Saklatvala.
Fondazione Ivo de Carneri ‘Forthe
promotion of control strategies against parasitic diseases in developing countries and to encourage
research in parasitology’
Professor Ivo de Carneri ( I927- 1993) was one of the great European parasitologists. Some will remember him as a laboratory scientist at NIMR (London, UK), The Carlo Erba Institute (Milan, Spain) and The Schiffs und Tropen Institute (Hamburg, Germany), while others will remember the enthusiasm he brought to field studies involving topics as diverse as cutaneous leishmaniasis in the Mato Gross0 and helminthiasis in Zanzibar. Perhaps his most lasting contribution, however, was as an educator; many young scientists acquired their first interest in parasitology through his teaching as Professor, and later as Chair of Parasitology at the University of Pavia, and through the courses in tropical medicine he initiated in developing countries. His classic book, Parassitologia General e Umona, is now in its I Ith edition - possibly a unique achievement for a university text in parasitology. The Fondazione Ivo de Carneri was established in October 1994; its objectives and activities include: l to promote research and training in parasite disease control through the construction of a public health laboratory in Pemba Island, Zanzibar, United Republic of Tanzania; l to encourage the study of parasitology by sustaining the revision and re-publication of Pcmssitologia General e Umana under the auspices of a Scientific Editorial Committee; l to support the development of young researchers from sub-Saharan Africa through the award of the Ivo de Carneri Prize for doctoral theses in parasitology. For more information on the Foundation, or to make a contribution towards its activities, please contact: Fondazione Ivo de Carneri, Via G Ceradini 3, 20 I29 Milano, Italy. Tel/Fax: +39 2738 1695.