Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-24T17:07:26.928Z Has data issue: false hasContentIssue false
  • English
  • Français

Schistosoma mansoni: larval damage and role of effector cell(s) in the synergy between vaccine immunity and Praziquantel treatment

Published online by Cambridge University Press:  06 April 2009

K. P. Piper ,
R. F. Mott ,
D. J. Hockley  and
D. J. McLaren
K. P. Piper
Affiliation:
Divisions of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA
R. F. Mott
Affiliation:
Mathematical Biology, National Institute for Medical Research, Mill Hill, London NW7 1AA
D. J. Hockley
Affiliation:
Electron Microscopy and Photography Section, National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Herts
D. J. McLaren
Affiliation:
Divisions of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA
Get access Rights & Permissions [Opens in a new window]

Abstract

A number of authors have demonstrated that the schistosomicidal compound, Praziquantel (Pzq), depends for its action upon the immune status of the host (Sabah et al. 1985; Brindley & Sher, 1987; Doenhoff et al. 1987). We have attempted to define the synergistic interaction between immuno- and chemotherapy further, using the murine irradiated vaccine model of schistosomiasis mansoni. In vaccinated mice, resistance operates in the skin but not the lungs; drug targeted towards lung-stage worms exacerbates lung-phase immunity, however, as depicted by the increased number and size of inflammatory reactions in the pulmonary tissues. Parasites are often found trapped within such foci. In the present investigation, light and ultrastructural studies have been utilized to examine the nature and extent of damage inflicted upon lung-stage larvae recovered from day 6 Pzq-treated vaccinated mice. Such studies have revealed that damage involves muscle disorganization, internal disruption and occasionally, loss of the tegument; in the latter case, cells are often seen attached to the denuded lung worms. To identify the crucial cellular effector cell(s) involved in the synergy between immuno- and chemotherapy, cell depletion studies have been performed in vivo. It would appear from these experiments that eosinophils or lymphocytes rather than neutrophils or macrophages are important effector cells in this synergy. Histological studies argue in favour of eosinophils being the key effector cells.

Keywords

Schistosoma mansoniimmunityvaccinationchemotherapyleucocyte ablationpraziquantelmorphologydamagesynergistic interactioneffector cells
Type
Research Article
Information
Parasitology , Volume 103 , Issue 2 , October 1991 , pp. 207 - 224
Copyright
Copyright © Cambridge University Press 1991

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aitken, R., Coulson, P. S., Dixon, B. & Wilson, R. A. (1987). Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 37, 570–7.Google Scholar
Allison, A. C. (1976). Fluorescence microscopy of lymphocytes and mononuclear phagocytes and the use of silica to eliminate the latter. In In Vitro Methods in Cell Mediated and Tumor Immunity (ed. Bloom, B. & David, J.), pp. 395–404. New York: Academic Press Inc.Google Scholar
Allison, A. C. & Hart, P. D'Arcy (1968). Potentiation by silica of growth of Mycobacterium tuberculosis in macrophage culture. British Journal of Experimental Pathology 49, 465–76.Google Scholar
Andrews, P. (1985). Praziquantel: mechanisms of anti-schistosomal activity. Pharmacology and Therapeutics 29, 129–56.Google Scholar
Becker, B., Mehlhorn, H., Andrews, P., Thomas, H. & Eckert, J. (1980). Light and electron microscopic studies on the effect of praziquantel on Schistosoma mansoni, Dicrocoelium dendriticum, and Fasciola hepatica (Trematoda) in vitro. Zeitschrift für Parasitenkunde 63, 113–28.Google Scholar
Brindley, P. J. & Sher, A. (1987). The chemotherapeutic effect of praziquantel against Schistosoma mansoni is dependent on host antibody response. Journal of Immunology 139, 215–20.Google Scholar
Brindley, P. J. & Sher, A. (1990). Immunological involvement in the efficacy of Praziquantel. Experimental Parasitology 71, 245–8.Google Scholar
Cawley, S., Findon, G. & Miller, T. E. (1988). Peripheral blood leukocyte count as an index of defence status in the leukopenic host. Journal of Laboratory Clinical Medicine 112, 52–7.Google Scholar
Delgado, V. S. (1989). Comparative studies of immune expression in the mouse and guinea pig models of Schistosomiasis mansoni and of the inter-relationship between immunity and drug therapy. Ph.D. thesis, Brunel University, Uxbridge, Middlesex, U.K.Google Scholar
Delgado, V. S. & McLaren, D. J. (1990). Evidence that radio-sensitive cells are central to skin phase immunity in CBA/Ca mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni as well as in naive mice protected with vaccine serum. Parasitology 100, 45–56.Google Scholar
Doenhoff, M. J., Sabah, A. A., Fletcher, C., Webbe, G. & Bain, J. (1987). Evidence for an immune-dependent action of Praziquantel on Schistosoma mansoni in mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 947–51.Google Scholar
Doenhoff, M. J., Modha, J. & Lambertucci, J. R. (1988). Anti-schistosome chemotherapy enhanced by antibodies specific for a parasite esterase. Immunology 65, 507–10.Google Scholar
Flisser, A. & McLaren, D. J. (1989). Effect of Praziquantel treatment on lung stage larvae of Schistosoma mansoni in vivo. Parasitology 98, 203–11.Google Scholar
Flisser, A., Delgado, V. S. & McLaren, D. J. (1989). Schistosoma mansoni: enhanced efficacy of Praziquantel treatment in immune mice. Parasite Immunology 11, 319–28.Google Scholar
Groll, E. (1984). Praziquantel. Advances in Pharmacology and Chemotherapy 20, 219–35.Google Scholar
Gutteridge, W. E. (1989). Parasite vaccines versus anti-parasite drugs: rivals or running mates? Parasitology 98, S87–S97.Google Scholar
Harnett, W. & Kusel, J. R. (1986). Increased exposure of parasite antigens at the surface of adult male Schistosoma mansoni exposed to praziquantel in vitro. Parasitology 93, 401–5.Google Scholar
Hockley, D. J. & McLaren, D. J. (1973). Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm. International Journal for Parasitology 3, 13–25.Google Scholar
James, S. L., Leonard, E. J. & Meltzer, M. S. (1982). Macrophages as effector cells of protective immunity in murine schistosomiasis. IV. Coincident induction of macrophage activation for extracellular killing of schistosomula and tumour cells. Cellular Immunology 74, 86–96.Google Scholar
Kamiya, H., Smithers, S. R. & McLaren, D. J. (1987). Schistosoma mansoni: autoradiographic tracking studies of isotopically labelled challenge parasites in naive and vaccinated CBA/Ca mice. Parasite Immunology 9, 515–29.Google Scholar
Keller, R. (1973). Cytostatic elimination of syngeneic rat tumor cells in vitro by nonspecifically activated macrophages. Journal of Experimental Medicine 138, 625–44.Google Scholar
Lopez, A. F., Strath, M. & Sanderson, C. J. (1984). Differentiation antigens on mouse eosinophils and neutrophils identified by monoclonal antibodies. British Journal of Haematology 57, 489–94.Google Scholar
McLaren, D. J. (1989). Will the real target of immunity to schistosomiasis please stand up. Parasitology Today 5, 279–82.Google Scholar
McLaren, D. J., Pearce, E. J. & Smithers, S. R. (1985). Site potential for challenge attrition in mice, rats and guinea pigs vaccinated with irradiated cercariae of Schistosoma mansoni. Parasite Immunology 7, 29–44.Google Scholar
McLaren, D. J., Strath, M. & Smithers, S. R. (1987). Schistosoma mansoni: evidence that immunity in vaccinated and chronically infected CBA/Ca mice is sensitive to treatment with a monoclonal antibody that depletes cutaneous effector cells. Parasite Immunology 9, 667–82.Google Scholar
McLaren, D. J. & Terry, R. J. (1982). The protective role of acquired host antigens during schistosome maturation. Parasite Immunology 4, 129–48.Google Scholar
Mehlhorn, H., Becker, B., Andrews, P., Thomas, H. & Frenkel, J. K. (1981). In vivo and in vitro experiments on the effects of praziquantel on Schistosoma mansoni. Arzneimittel Forschung/Drug Research 31, 544–54.Google Scholar
Modha, J., Lambertucci, J. R., Doenhoff, M. J. & McLaren, D. J. (1990). Immune dependence of schistosomicidal chemotherapy: an ultrastructural study of Schistosoma mansoni adult worms exposed to Praziquantel and immune serum in vivo. Parasite Immunology 12, 321–34.Google Scholar
Pax, R., Bennett, J. L. & Fetterer, R. (1978). A benzodiazepine derivative and praziquantel: effects on musculature of Schistosoma mansoni and Schistosoma japonicum. Naunyn-Schmiedeberg's Archives of Pharmacology 304, 309–15.Google Scholar
Piper, K. P., Mott, R. F. & McLaren, D. J. (1990). Schistosoma mansoni: histological analysis of the synergistic interaction between vaccine immunity and Praziquantel therapy in the lungs of mice. Parasite Immunology 12, 367–87.Google Scholar
Rios, A. & Simmons, R. L. (1972). Poly-2-vinylpyridine-N-oxide reverses the immunosuppressive effects of silica and carrageenan. Transplantation 13, 343–5.Google Scholar
Sabah, A. A., Fletcher, C., Webbe, G. & Doenhoff, M. J. (1985). Schistosoma mansoni: reduced efficacy of chemotherapy in infected T-cell deprived mice. Experimental Parasitology 60, 348–54.Google Scholar
Shaw, M. K. & Erasmus, D. A. (1982). Schistosoma mansoni: effects of praziquantel on the ultrastructure of worms in vivo. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 528.Google Scholar
Shaw, M. K. & Erasmus, D. A. (1983 a). Schistosoma mansoni: The effects of a subcurative dose of praziquantel on the ultrastructure of worms in vivo. Zeitschrift für Parasitenkunde 69, 73–90.Google Scholar
Shaw, M. K. & Erasmus, D. A. (1983 b). Schistosoma mansoni: dose-related tegumental surface changes after in vivo treatment with praziquantel. Zeitschrift für Parasitenkunde 69, 643–53.Google Scholar
Shaw, M. K. & Erasmus, D. A. (1987). Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with Praziquantel. Parasitology 94, 243–54.Google Scholar
Smithers, S. R. & Gammage, K. (1980). The recovery of Schistosoma mansoni from the skin, lungs and hepatic portal system of naive mice and mice previously exposed to S. mansoni: evidence for two phases of parasite attrition in immune mice. Parasitology 80, 289–300.Google Scholar
Smithers, S. R. & Terry, R. J. (1965). The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitology 55, 695–700.Google Scholar
Vignali, D. A. A., Bickle, Q. D. & Taylor, M. G. (1988). Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice. Parasitology 96, 49–61.Google Scholar
Ward, R. E. M. & McLaren, D. J. (1988). Schistosoma mansoni: evidence that eosinophils and/or macrophages contribute to skin phase challenge attrition in vaccinated CBA/Ca mice. Parasitology 96, 63–84.Google Scholar