Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 Mar;63(3):940–945. doi: 10.1128/iai.63.3.940-945.1995

Impact of microfilaremia on maintenance of a hyporesponsive cellular immune response in Brugia-infected gerbils (Meriones unguiculatus).

S C Bosshardt 1, S U Coleman 1, C S McVay 1, K L Jones 1, T R Klei 1
PMCID: PMC173093  PMID: 7868266

Abstract

The purpose of these experiments was to define the significance of the microfilarial stage to the hyporesponsive condition seen in lymphatic filariasis. Two types of experiments were conducted with Brugia pahangi-infected gerbils. In one, in vitro lymphocyte blastogenesis and in vivo granuloma formation in response to parasite antigen were correlated to microfilaremia in chronically infected individuals. In a second set of experiments, the level of in vivo granuloma formation was assessed following chemotherapeutic removal of microfilariae with ivermectin. The results indicated that the microfilarial stage alone is not responsible for the maintenance of the low cellular responses seen during chronic infections in this model. Furthermore, the data suggest that the degree of downregulation of these responses may be related to parasite burden.

Full Text

The Full Text of this article is available as a PDF (205.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bosshardt S. C., McVay C. S., Coleman S. U., Klei T. R. Brugia pahangi: effects of maternal filariasis on the responses of their progeny to homologous challenge infection. Exp Parasitol. 1992 May;74(3):271–282. doi: 10.1016/0014-4894(92)90150-9. [DOI] [PubMed] [Google Scholar]
  2. Denham D. A., Medeiros F., Baldwin C., Kumar H., Midwinter I. C., Birch D. W., Smail A. Repeated infection of cats with Brugia pahangi: parasitological observations. Parasitology. 1992 Jun;104(Pt 3):415–420. doi: 10.1017/s0031182000063666. [DOI] [PubMed] [Google Scholar]
  3. Horii Y., Nakanishi H., Mori A., Zaitsu M., Ueda M., Kurokawa K., Oda T., Fujita K. Eosinophil hyporesponse of jirds induced by microfilariae of Brugia pahangi. Am J Trop Med Hyg. 1989 Aug;41(2):183–188. doi: 10.4269/ajtmh.1989.41.183. [DOI] [PubMed] [Google Scholar]
  4. King C. L., Mahanty S., Kumaraswami V., Abrams J. S., Regunathan J., Jayaraman K., Ottesen E. A., Nutman T. B. Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J Clin Invest. 1993 Oct;92(4):1667–1673. doi: 10.1172/JCI116752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Klei T. R., McVay C. S., Dennis V. A., Coleman S. U., Enright F. M., Casey H. W. Brugia pahangi: effects of duration of infection and parasite burden on lymphatic lesion severity, granulomatous hypersensitivity, and immune responses in jirds (Meriones unguiculatus). Exp Parasitol. 1990 Nov;71(4):393–405. doi: 10.1016/0014-4894(90)90065-k. [DOI] [PubMed] [Google Scholar]
  6. Lal R. B., Kumaraswami V., Steel C., Nutman T. B. Phosphocholine-containing antigens of Brugia malayi nonspecifically suppress lymphocyte function. Am J Trop Med Hyg. 1990 Jan;42(1):56–64. doi: 10.4269/ajtmh.1990.42.56. [DOI] [PubMed] [Google Scholar]
  7. Lammie P. J., Eberhard M. L., Leiva L. E., Lowrie R. C., Jr, Katz S. P. The effect of diethylcarbamazine treatment of Bancroftian filariasis on the immunological reactivity of microfilaraemic individuals. Trans R Soc Trop Med Hyg. 1988;82(5):726–729. doi: 10.1016/0035-9203(88)90216-7. [DOI] [PubMed] [Google Scholar]
  8. Lammie P. J., Hightower A. W., Richards F. O., Jr, Bryan R. T., Spencer H. C., McNeeley D. F., McNeeley M. B., Eberhard M. L. Alterations in filarial antigen-specific immunologic reactivity following treatment with ivermectin and diethylcarbamazine. Am J Trop Med Hyg. 1992 Mar;46(3):292–295. doi: 10.4269/ajtmh.1992.46.292. [DOI] [PubMed] [Google Scholar]
  9. Lammie P. J., Katz S. P. Immunoregulation in experimental filariasis. II. Responses to parasite and nonparasite antigens in jirds with Brugia pahangi. J Immunol. 1983 Mar;130(3):1386–1389. [PubMed] [Google Scholar]
  10. Lammie P. J., Leiva L. E., Ruff A. J., Eberhard M. L., Lowrie R. C., Jr, Katz S. P. Bancroftian filariasis in Haiti: preliminary characterization of the immunological responsiveness of microfilaremic individuals. Am J Trop Med Hyg. 1988 Jan;38(1):125–129. doi: 10.4269/ajtmh.1988.38.125. [DOI] [PubMed] [Google Scholar]
  11. Leiva L. E., Lammie P. J. Modulation of lymphocyte activation by soluble Brugia pahangi extracts. Trop Med Parasitol. 1989 Sep;40(3):327–331. [PubMed] [Google Scholar]
  12. Maizels R. M., Lawrence R. A. Immunological tolerance: The key feature in human filariasis? Parasitol Today. 1991 Oct;7(10):271–276. doi: 10.1016/0169-4758(91)90093-4. [DOI] [PubMed] [Google Scholar]
  13. McVay C. S., Klei T. R., Coleman S. U., Bosshardt S. C. A comparison of host responses of the Mongolian jird to infections of Brugia malayi and B. pahangi. Am J Trop Med Hyg. 1990 Sep;43(3):266–273. doi: 10.4269/ajtmh.1990.43.266. [DOI] [PubMed] [Google Scholar]
  14. Miller S., Schreuer D., Hammerberg B. Inhibition of antigen-driven proliferative responses and enhancement of antibody production during infection with Brugia pahangi. J Immunol. 1991 Aug 1;147(3):1007–1013. [PubMed] [Google Scholar]
  15. Nutman T. B., Kumaraswami V., Ottesen E. A. Parasite-specific anergy in human filariasis. Insights after analysis of parasite antigen-driven lymphokine production. J Clin Invest. 1987 May;79(5):1516–1523. doi: 10.1172/JCI112982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pearlman E., Hazlett F. E., Jr, Boom W. H., Kazura J. W. Induction of murine T-helper-cell responses to the filarial nematode Brugia malayi. Infect Immun. 1993 Mar;61(3):1105–1112. doi: 10.1128/iai.61.3.1105-1112.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Petit T. A., Coleman S. U., Jones K. L., Enright F. M., Klei T. R. Brugia pahangi: effects of protective resistance on lymphatic lesions and granulomatous inflammation in infected jirds (Meriones unguiculatus). Exp Parasitol. 1993 Dec;77(4):395–404. doi: 10.1006/expr.1993.1099. [DOI] [PubMed] [Google Scholar]
  18. Piessens W. F., McGreevy P. B., Piessens P. W., McGreevy M., Koiman I., Saroso J. S., Dennis D. T. Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens. J Clin Invest. 1980 Jan;65(1):172–179. doi: 10.1172/JCI109648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Piessens W. F., Ratiwayanto S., Piessens P. W., Tuti S., McGreevy P. B., Darwis F., Palmieri J. R., Koiman I., Dennis D. T. Effect of treatment with diethylcarbamazine on immune responses to filarial antigens in patients infected with Brugia malayi. Acta Trop. 1981 Sep;38(3):227–234. [PubMed] [Google Scholar]
  20. Rao U. R., Kwa B. H., Nayar J. K., Vickery A. C. Brugia malayi and Brugia pahangi: transmission blocking activity of ivermectin and brugian filarial infections in Aedes aegypti. Exp Parasitol. 1990 Oct;71(3):259–266. doi: 10.1016/0014-4894(90)90030-g. [DOI] [PubMed] [Google Scholar]
  21. Richards F. O., Jr, Eberhard M. L., Bryan R. T., McNeeley D. F., Lammie P. J., McNeeley M. B., Bernard Y., Hightower A. W., Spencer H. C. Comparison of high dose ivermectin and diethylcarbamazine for activity against bancroftian filariasis in Haiti. Am J Trop Med Hyg. 1991 Jan;44(1):3–10. doi: 10.4269/ajtmh.1991.44.3. [DOI] [PubMed] [Google Scholar]
  22. Schreuer D., Hammerberg B. Modulation of cellular and humoral immunity, and disease manifestation during onset of patency in Brugia pahangi-infected dogs. Immunology. 1993 Aug;79(4):658–666. [PMC free article] [PubMed] [Google Scholar]
  23. Secor W. E. Sizing up granulomas. Exp Parasitol. 1994 May;78(3):336–339. doi: 10.1006/expr.1994.1036. [DOI] [PubMed] [Google Scholar]
  24. Soboslay P. T., Dreweck C. M., Hoffmann W. H., Lüder C. G., Heuschkel C., Görgen H., Banla M., Schulz-Key H. Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment. Clin Exp Immunol. 1992 Sep;89(3):407–413. doi: 10.1111/j.1365-2249.1992.tb06971.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Soboslay P. T., Lüder C. G., Hoffmann W. H., Michaelis I., Helling G., Heuschkel C., Dreweck C. M., Blanke C. H., Pritze S., Banla M. Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection. Clin Exp Immunol. 1994 May;96(2):238–244. doi: 10.1111/j.1365-2249.1994.tb06548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vincent A. L., Ash L. R. Splenomegaly in jirds (Meriones unguiculatus) infected with Brugia malavi (Nematoda: Filarioidea) and related species. Am J Trop Med Hyg. 1978 May;27(3):514–520. doi: 10.4269/ajtmh.1978.27.514. [DOI] [PubMed] [Google Scholar]
  27. Wadee A. A., Vickery A. C., Piessens W. F. Characterization of immunosuppressive proteins of Brugia malayi microfilariae. Acta Trop. 1987 Sep;44(3):343–352. [PubMed] [Google Scholar]
  28. Weil G. J., Chandrashekar R., Liftis F., McVay C. S., Bosshardt S. C., Klei T. R. Circulating parasite antigen in Brugia pahangi-infected jirds. J Parasitol. 1990 Feb;76(1):78–84. [PubMed] [Google Scholar]
  29. Weil G. J., Lammie P. J., Richards F. O., Jr, Eberhard M. L. Changes in circulating parasite antigen levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin. J Infect Dis. 1991 Oct;164(4):814–816. doi: 10.1093/infdis/164.4.814. [DOI] [PubMed] [Google Scholar]
  30. Wenger J. D., Forsyth K. P., Kazura J. W. Identification of phosphorylcholine epitope-containing antigens in Brugia malayi and relation of serum epitope levels to infection status of jirds with brugian filariasis. Am J Trop Med Hyg. 1988 Jan;38(1):133–141. doi: 10.4269/ajtmh.1988.38.133. [DOI] [PubMed] [Google Scholar]
  31. Yazdanbakhsh M., Paxton W. A., Kruize Y. C., Sartono E., Kurniawan A., van het Wout A., Selkirk M. E., Partono F., Maizels R. M. T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis. J Infect Dis. 1993 Apr;167(4):925–931. doi: 10.1093/infdis/167.4.925. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES