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Eosinophils are the major effector cells of immunity to microfilariae in a mouse model of onchocerciasis

Published online by Cambridge University Press:  06 April 2009

S. G. Folkard
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
P. J. Hogarth
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
M. J. Taylor
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
A. E. Bianco
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK

Summary

Mice inoculated with microfilariae of the filarial nematode Onchocerca lienalis clear their parasites over a period of 3–4 months and are highly resistant to re-infection. We have investigated the comparative roles of the eosinophil, macrophage and neutrophil in effecting this parasite clearance, employing agents specifically to perturb cell function in vivo. Using the anti-IL-5 monoclonal antibody TRFK-5, we show that eosinophils are of primary importance in effecting resistance to re-infection. Ablation of macrophages (with carbon) and neutrophils (with the monoclonal antibody NIMP-R14) had no effect on parasite clearance following re-infection. Neutralization of these 3 cell types during a primary infection showed that while the removal of both eosinophils and macrophages caused a small but significant delay in parasite clearance, the depletion of neutrophils had no effect. This report describes the first direct evidence for eosinophil-mediated killing of microfilariae in vivo, and is consistent with Th-2 cell responses previously described in this model.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

Ackerman, S. J., Kephart, G. M., Francis, H., Awadzi, K., Gleich, G. J. & Ottesen, E. A. (1990). Eosinophil degranulation: an immunologic determinant in the pathogenesis of the Mazzotti Reaction in human onchocerciasis. Journal of Immunology 144, 3961–9.CrossRefGoogle ScholarPubMed
Bianco, A. E. (1991). Onchocerciasis. In Parasitic Helminths and Zoonoses in Africa (ed. MacPherson, C. N. L. & Craig, P. S.), pp. 138189. London: Unwin Hyman Press.Google Scholar
Bianco, A. E., Ham, P. J., Sinnary, E. L. & Nelson, G. S. (1980). Large-scale recovery of Onchocerca microfilariae from naturally infected cattle and horses. Transactions of the Royal Society for Tropical Medicine and Hygiene 74, 109–10.Google Scholar
Bianco, A. E., Luty, A., Whitworth, J. & Taylor, D. (1991). Immunity to Onchocerca volvulus microfilariae in mice and the induction of cross-protection with O. lienalis. Tropical Medicine and Parasitology 42, 188–90.Google ScholarPubMed
Brattig, N. W., Tischendorf, F. W., Strote, G. & Medina-De-La-Garza, C. E. (1991). Eosinophil–larval interaction in onchocerciasis: heterogeneity of in vitro adherence of eosinophils to infective third and fourth stage larvae and microfilariae of Onchocerca volvulus. Parasite Immunology 13, 1322.CrossRefGoogle ScholarPubMed
Butterworth, A. E. (1984). Cell-mediated damage to helminths. In Advances in Parasitology Vol. 23 (ed. Baker, J. R. & Muller, R.), pp. 143235. London: Academic Press.Google Scholar
Buttner, D. W., Laer, G. V., Mannweiler, E. & Buttner, M. (1982). Clinical, parasitological and serological studies on onchocerciasis in the Yemen Arab Republic. Tropical Medicine and Parasitology 33, 201–12.Google ScholarPubMed
Carlow, C. K. S. & Bianco, A. E. (1987). Transfer of immunity to the microfilariae of Onchocerca lienalis in mice. Tropical Medicine and Parasitology 39, 283–6.Google Scholar
Carlow, C. K. S., Dobinson, A. R. & Bianco, A. E. (1988). Parasite-specific immune responses to Onchocerca lienalis microfilariae in normal and immunodeficient mice. Parasite Immunology 10, 309–22.CrossRefGoogle ScholarPubMed
Cheever, A. W., Finkelman, F. D., Caspar, P., Heiny, S., Macedonia, J. G. & Sher, A. (1992). Treatment with anti-IL-2 antibodies reduces hepatic pathology and eosinophilia in Schistosoma mansoni-infected mice while selectively inhibiting T cell IL-5 production. Journal of Immunology 148, 3244–8.CrossRefGoogle ScholarPubMed
Coffman, R. L., Seymour, B. W., Hudak, S., Jackson, J. & Rennick, D. (1989). Antibody to IL-5 inhibits helminth-induced eosinophilia in mice. Science 245, 308–1O.CrossRefGoogle ScholarPubMed
Connor, D. H., Gibson, D. W., Neafie, R. C., Merighi, B. & Buck, A. A. (1983). Sowda – onchocerciasis in north Yemen: a clinicopathologic study of 18 patients. American Journal for Tropical Medicine and Hygiene 32, 123–37.CrossRefGoogle ScholarPubMed
Elson, L. H., Calvopina, M. H., Paredes, W. Y., Araujo, E. N., Bradley, J. E., Guderian, R. H. & Nutman, T. B. (1995). Immunity to onchocerciasis: putative immune persons produce a Th1-like response to Onchocerca volvulus. Journal of Infectious Diseases 171, 652–8.CrossRefGoogle ScholarPubMed
Folkard, S. G. & Bianco, A. E. (1995). Roles for both CD4+ and CD8+ T cells in protective immunity against Onchocerca lienalis microfilariae in the mouse. Parasite Immunology 17.CrossRefGoogle ScholarPubMed
Gounni, A. S., Lamkhioued, B., Ochiai, K., Tanaka, Y., Delaporte, E., Capron, A., Kinet, J. -P. & Capron, M. (1994). High affinity IgE receptor on eosinophils is involved in defence against parasites. Nature, London 367, 183–6.CrossRefGoogle ScholarPubMed
Greene, B. M., Taylor, H. R. & Aikawa, M. (1981). Cellular killing of microfilariae of Onchocerca volvulus: eosinophil and neutrophil-mediated immune serum-dependent destruction. Journal of Immunology 127, 1611–18.CrossRefGoogle ScholarPubMed
Herndont, F. J. & Hayes, S. G. (1992). Depletion of eosinophils by and-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection. Journal of Immunology 149, 3642–7.CrossRefGoogle Scholar
Hogarth, P. J., Folkard, S. G., Taylor, M. J. & Bianco, A. E. (1995). Accelerated clearance of Onchocerca microfilariae and resistance to re-infection in interleukin-4 gene knockout mice. Parasite Immunology 17.CrossRefGoogle ScholarPubMed
Hudson, L. & Hay, F. C. (1991). Practical Immunology. Oxford: Blackwell Scientific Publications.Google Scholar
Johnson, E. H., Lustigman, S., Brotman, B., Browne, J. & Prince, A. M. (1991). Onchocerca volvulus: in vitro killing of microfilariae by neutrophils and eosinophils from experimentally infected chimpanzees. Tropical Medicine and Parasitology 42, 351–5.Google ScholarPubMed
Jones, R. E., Finkelman, F. D., Hester, R. B. & Kayes, S. G. (1994). Toxocara canis: failure to find IgE receptors (FcεR) on eosinophils from infected mice suggests that murine eosinophils do not kill helminth larvae by an IgE-dependent mechanism. Experimental Parasitology 78, 6475.CrossRefGoogle Scholar
King, C. L. & Nutman, T. B. (1991). Regulation of the immune response in lymphatic filariasis and onchocerciasis. In Immunoparasitology Today (ed. Ash, C. & Gallagher, R.), pp. A54–A58. Cambridge: Elsevier Trends Journals.Google Scholar
Korenaga, M., Hitoshi, Y., Yamaguchi, N., Sato, Y., Takatsu, K. & Tada, I. (1991). The role of interleukin-5 in protective immunity to Strongyloides venezuelensis infection in mice. Immunology 72, 502–7.Google ScholarPubMed
Lange, A. M., Yutanawiboonchai, W., Scott, P. & Abraham, D. (1994). IL-4 and IL-5-dependent protective immunity to Onchocerca volvulus infective larvae in BALB/cBYJ mice. Journal of Immunology 153, 205–11.CrossRefGoogle ScholarPubMed
Limaye, A. P., Abrams, J. S., Silver, J. E., Awadzi, K., Francis, H. F., Ottesen, E. A. & Nutman, T. B. (1991). Interleukin-5 and the post-treatment eosinophilia in patients with onchocerciasis. Journal of Clinical Investigation 88, 1418–21.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
Medina-De-La-Garza, C. E., Brattig, N. W., Tischendorf, F. W. & Jarret, J. M. B. (1990). Serum-dependent interaction of granulocytes with Onchocerca volvulus microfilariae in generalised and chronic hyper-reactive onchocerciasis and its modulation by diethylcarbamazine. Transactions of the Royal Society for Tropical Medicine and Hygiene 84, 701–6.CrossRefGoogle ScholarPubMed
Nakanishi, H., Horii, Y., Terashima, K. & Fujita, K. (1989). Effect of macrophage blockade on the resistance to a primary Brugia pahangi infection of female BALB/c mice. Tropical Medicine and Parasitology 40, 75–6.Google ScholarPubMed
Ngu, J. L. (1978). Immunological studies on onchocerciasis. Varying skin hypersensitivity and leukocyte migration inhibition in a clinical spectrum of the disease. Acta Tropica 35, 269–79.Google Scholar
Ottesen, E. A. (1995). Immune responsiveness and the pathogenesis of human onchocerciasis. Journal of Infectious Diseases 171, 659–71.CrossRefGoogle ScholarPubMed
Racz, P., Tenner-Racz, K., Buttner, D. W. & Albiez, E. J. (1982). Ultrastructural evidence for eosinophil– parasite adherence (EPA) reaction in human onchocercal lymphadenitis in the early period following diethylcarbamazine treatment. Tropenmedizin und Parasitologie 33, 213–18.Google ScholarPubMed
Sasaki, O., Sugaya, H., IshlDa, K. & Yoshimura, K. (1993). Ablation of eosinophils with anti-IL-5 antibody enhances the survival of Angiostrongylus cantonensis in the mouse. Journal of Immunology 15, 349–54.Google ScholarPubMed
Sher, A., Coffman, R. L., Hieny, S. & Cheever, A. W. (1990). Ablation of eosinophil and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. Journal of Immunology 45, 3911–16.CrossRefGoogle Scholar
Soboslay, P. T., Luder, C. G. K., Hoffmann, W. H., Michaelis, I., Helling, G., Heuschkel, C., Dreweck, C. M., Blanke, C. H., Pritze, S., Banla, M. & Schultz-Key, H. (1994). Ivermectin-facilitated immunity in onchocerciasis: activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection. Clinical and Experimental Immunology 96, 238–44.CrossRefGoogle ScholarPubMed
Steel, C. & Nutman, T. B. (1993). Regulation of IL-5 in onchocerciasis: a critical role for IL-2. Journal of Immunology 150, 5511–18.CrossRefGoogle ScholarPubMed
Takatsu, K. (1992). Interleukin-5. Current Opinion in Immunology 4, 299306.CrossRefGoogle ScholarPubMed
Taylor, M. J., Cross, H. F., Mohammed, A. A., Trees, A. J. & Bianco, A. E. (1996). Susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to nitric oxide and hydrogen peroxide in cell-free culture and from IFNγ-activated macrophages. Parasitology 112, 315–22.CrossRefGoogle Scholar
Townson, S. & Bianco, A. E. (1982). Experimental infection of mice with the microfilariae of Onchocerca lienalis. Parasitology 85, 283–93.CrossRefGoogle ScholarPubMed
Vanrooijen, N. & Sanders, A. (1994). Liposome-mediated depletion of macrophages – mechanism of action, preparation of liposomes and applications. Journal of Immunological Methods 174, 8393.Google Scholar
Ward, D. J., Nutman, T. B., Zea-Flores, G., Portocarrero, C., Lujan, A. & Ottesen, E. A. (1988). Onchocerciasis and immunity in humans: enhanced T cell responsiveness to parasite antigen in putatively immune individuals. Journal of Infectious Diseases 157, 536–43.CrossRefGoogle ScholarPubMed
Ware, C. F., Donato, N. J. & Dorshkind, K. (1985). Human, rat or mouse hybridomas secrete high levels of monoclonal antibodies following transplantation into mice with severe combined immunodeficiency disease (SCID). Journal of Immunological Methods 85, 353–61.CrossRefGoogle ScholarPubMed
Wildenberg, G, Darge, K., Knab, J., Tischendorf, F. W., Bonow, I. & Buttner, D. W. (1994). Lymph nodes of onchocerciasis patients after treatment with ivermectin: reaction of eosinophil granulocytes and their cationic granule proteins. Tropical Medicine and Parasitology 45, 8796.Google Scholar
Yamaguchi, Y., Matsui, T., Kasahara, T., Etho, S., Tominaga, A., Takatsu, K., Miura, Y. & Suda, T. (1990). In vivo changes of hemopoietic progenitors and the expression of interleukin 5 (IL-5) gene in eosinophilic mice infected with Toxocara canis. Experimental Haematology 18, 1152–7.Google ScholarPubMed