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. 1998 Nov;95(3):488–493. doi: 10.1046/j.1365-2567.1998.00620.x

Regulation of primary Strongyloides ratti infections in mice: a role for interleukin-5.

K S Ovington 1, K McKie 1, K I Matthaei 1, I G Young 1, C A Behm 1
PMCID: PMC1364418  PMID: 9824515

Abstract

C57BL/6 mice genetically deficient in interleukin-5 (IL-5-/-) and normal C57BL/6 (IL-5+/+) mice were infected with larvae of a homogonic strain of the nematode Strongyloides ratti. In primary infections both male and female IL-5-/- mice released two to four times more eggs and larvae than IL-5+/+ mice. IL-5-/- mice harboured about 60% more intestinal worms, which were more fecund, than IL-5+/+ mice. The duration of the infection was similar in normal and IL-5-deficient mice. Both IL-5-/- and IL-5+/+ mice resisted a secondary infection. IL5-/- mice lost more weight during the infection than normal mice and took longer to regain their initial weight after expelling the worms. The number of eosinophils increased in the bone marrow, peritoneal cavity and small intestine of IL-5+/+ mice, but not IL-5-/- mice, following infection. No significant differences between infected IL-5+/+ and IL-5-/- mice in mast cells or other leucocytes were observed in the peritoneal cavity. Thus, IL-5 functions to protect the host in a primary infection of S. ratti by limiting the number and fecundity of worms establishing in the small intestine. This protection is correlated with elevated blood and tissue eosinophilia which occurs in normal mice but not in IL-5-/- mice.

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Selected References

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  1. Abe T., Sugaya H., Yoshimura K. Different susceptibility to the IL-3 induced-protective effects between Strongyloides ratti and Nippostrongylus brasiliensis in C57BL/6 mice. Parasite Immunol. 1993 Nov;15(11):643–645. doi: 10.1111/j.1365-3024.1993.tb00578.x. [DOI] [PubMed] [Google Scholar]
  2. Ackerman S. J., Kephart G. M., Francis H., Awadzi K., Gleich G. J., Ottesen E. A. Eosinophil degranulation. An immunologic determinant in the pathogenesis of the Mazzotti reaction in human onchocerciasis. J Immunol. 1990 May 15;144(10):3961–3969. [PubMed] [Google Scholar]
  3. Bao S., Beagley K. W., Murray A. M., Caristo V., Matthaei K. I., Young I. G., Husband A. J. Intestinal IgA plasma cells of the B1 lineage are IL-5 dependent. Immunology. 1998 Jun;94(2):181–188. doi: 10.1046/j.1365-2567.1998.00512.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Behnke J. M., Wahid F. N., Grencis R. K., Else K. J., Ben-Smith A. W., Goyal P. K. Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): downregulation of specific cytokine secretion (IL-9 and IL-10) correlates with poor mastocytosis and chronic survival of adult worms. Parasite Immunol. 1993 Jul;15(7):415–421. doi: 10.1111/j.1365-3024.1993.tb00626.x. [DOI] [PubMed] [Google Scholar]
  5. Butterworth A. E. Cell-mediated damage to helminths. Adv Parasitol. 1984;23:143–235. doi: 10.1016/s0065-308x(08)60287-0. [DOI] [PubMed] [Google Scholar]
  6. Butterworth A. E., Dalton P. R., Dunne D. W., Mugambi M., Ouma J. H., Richardson B. A., Siongok T. K., Sturrock R. F. Immunity after treatment of human schistosomiasis mansoni. I. Study design, pretreatment observations and the results of treatment. Trans R Soc Trop Med Hyg. 1984;78(1):108–123. doi: 10.1016/0035-9203(84)90190-1. [DOI] [PubMed] [Google Scholar]
  7. Carroll S. M., Mayrhofer G., Dawkins H. J., Grove D. I. Kinetics of intestinal lamina propria mast cells, globule leucocytes, intraepithelial lymphocytes, goblet cells and eosinophils in murine strongyloidiasis. Int Arch Allergy Appl Immunol. 1984;74(4):311–317. doi: 10.1159/000233566. [DOI] [PubMed] [Google Scholar]
  8. Cheever A. W., Xu Y. H., Sher A., Macedonia J. G. Analysis of egg granuloma formation in Schistosoma japonicum-infected mice treated with antibodies to interleukin-5 and gamma interferon. Infect Immun. 1991 Nov;59(11):4071–4074. doi: 10.1128/iai.59.11.4071-4074.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coffman R. L., Seymour B. W., Hudak S., Jackson J., Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308–310. doi: 10.1126/science.2787531. [DOI] [PubMed] [Google Scholar]
  10. Dawkins H. J., Grove D. I., Dunsmore J. D., Mitchell G. F. Strongyloides ratti: susceptibility to infection and resistance to reinfection in inbred strains of mice as assessed by excretion of larvae. Int J Parasitol. 1980 Apr;10(2):125–129. doi: 10.1016/0020-7519(80)90023-5. [DOI] [PubMed] [Google Scholar]
  11. Dawkins H. J., Robertson T. A., Papadimitriou J. M., Grove D. I. Light and electron microscopical studies of the location of Strongyloides ratti in the mouse intestine. Z Parasitenkd. 1983;69(3):357–370. doi: 10.1007/BF00927877. [DOI] [PubMed] [Google Scholar]
  12. Dawkins H. J., Thomason H. J., Grove D. I. The occurrence of Strongyloides ratti in the tissues of mice after percutaneous infection. J Helminthol. 1982 Mar;56(1):45–50. doi: 10.1017/s0022149x00034994. [DOI] [PubMed] [Google Scholar]
  13. Folkard S. G., Hogarth P. J., Taylor M. J., Bianco A. E. Eosinophils are the major effector cells of immunity to microfilariae in a mouse model of onchocerciasis. Parasitology. 1996 Mar;112(Pt 3):323–329. doi: 10.1017/s0031182000065847. [DOI] [PubMed] [Google Scholar]
  14. Foster P. S., Hogan S. P., Ramsay A. J., Matthaei K. I., Young I. G. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996 Jan 1;183(1):195–201. doi: 10.1084/jem.183.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hagan P., Moore P. J., Adjukiewicz A. B., Greenwood B. M., Wilkins H. A. In-vitro antibody-dependent killing of schistosomula of Schistosoma haematobium by human eosinophils. Parasite Immunol. 1985 Nov;7(6):617–624. doi: 10.1111/j.1365-3024.1985.tb00105.x. [DOI] [PubMed] [Google Scholar]
  16. Hagan P., Wilkins H. A., Blumenthal U. J., Hayes R. J., Greenwood B. M. Eosinophilia and resistance to Schistosoma haematobium in man. Parasite Immunol. 1985 Nov;7(6):625–632. doi: 10.1111/j.1365-3024.1985.tb00106.x. [DOI] [PubMed] [Google Scholar]
  17. Herndon F. J., Kayes S. G. Depletion of eosinophils by anti-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection. J Immunol. 1992 Dec 1;149(11):3642–3647. [PubMed] [Google Scholar]
  18. Johnson E. H., Lustigman S., Brotman B., Browne J., Prince A. M. Onchocerca volvulus: in vitro killing of microfilaria by neutrophils and eosinophils from experimentally infected chimpanzees. Trop Med Parasitol. 1991 Dec;42(4):351–355. [PubMed] [Google Scholar]
  19. Kopf M., Brombacher F., Hodgkin P. D., Ramsay A. J., Milbourne E. A., Dai W. J., Ovington K. S., Behm C. A., Köhler G., Young I. G. IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity. 1996 Jan;4(1):15–24. doi: 10.1016/s1074-7613(00)80294-0. [DOI] [PubMed] [Google Scholar]
  20. Korenaga M., Hitoshi Y., Takatsu K., Tada I. Cross-resistance between Strongyloides venezuelensis and S. ratti in mice. J Helminthol. 1995 Jun;69(2):119–123. doi: 10.1017/s0022149x00014000. [DOI] [PubMed] [Google Scholar]
  21. Korenaga M., Hitoshi Y., Takatsu K., Tada I. Regulatory effect of anti-interleukin-5 monoclonal antibody on intestinal worm burden in a primary infection with strongyloides venezuelensis in mice. Int J Parasitol. 1994 Nov;24(7):951–957. doi: 10.1016/0020-7519(94)90159-7. [DOI] [PubMed] [Google Scholar]
  22. Korenaga M., Hitoshi Y., Yamaguchi N., Sato Y., Takatsu K., Tada I. The role of interleukin-5 in protective immunity to Strongyloides venezuelensis infection in mice. Immunology. 1991 Apr;72(4):502–507. [PMC free article] [PubMed] [Google Scholar]
  23. Lange A. M., Yutanawiboonchai W., Scott P., Abraham D. IL-4- and IL-5-dependent protective immunity to Onchocerca volvulus infective larvae in BALB/cBYJ mice. J Immunol. 1994 Jul 1;153(1):205–211. [PubMed] [Google Scholar]
  24. Lantz C. S., Boesiger J., Song C. H., Mach N., Kobayashi T., Mulligan R. C., Nawa Y., Dranoff G., Galli S. J. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature. 1998 Mar 5;392(6671):90–93. doi: 10.1038/32190. [DOI] [PubMed] [Google Scholar]
  25. Matthaei K. I., Foster P., Young I. G. The role of interleukin-5 (IL-5) in vivo: studies with IL-5 deficient mice. Mem Inst Oswaldo Cruz. 1997;92 (Suppl 2):63–68. doi: 10.1590/s0074-02761997000800010. [DOI] [PubMed] [Google Scholar]
  26. Mauser P. J., Pitman A. M., Fernandez X., Foran S. K., Adams G. K., 3rd, Kreutner W., Egan R. W., Chapman R. W. Effects of an antibody to interleukin-5 in a monkey model of asthma. Am J Respir Crit Care Med. 1995 Aug;152(2):467–472. doi: 10.1164/ajrccm.152.2.7633694. [DOI] [PubMed] [Google Scholar]
  27. Medina-De la Garza C. E., Brattig N. W., Tischendorf F. W., Jarrett J. M. Serum-dependent interaction of granulocytes with Onchocerca volvulus microfilariae in generalized and chronic hyper-reactive onchocerciasis and its modulation by diethylcarbamazine. Trans R Soc Trop Med Hyg. 1990 Sep-Oct;84(5):701–706. doi: 10.1016/0035-9203(90)90155-8. [DOI] [PubMed] [Google Scholar]
  28. Mould A. W., Matthaei K. I., Young I. G., Foster P. S. Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice. J Clin Invest. 1997 Mar 1;99(5):1064–1071. doi: 10.1172/JCI119234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ovington K. S., Behm C. A. The enigmatic eosinophil: investigation of the biological role of eosinophils in parasitic helminth infection. Mem Inst Oswaldo Cruz. 1997;92 (Suppl 2):93–104. doi: 10.1590/s0074-02761997000800013. [DOI] [PubMed] [Google Scholar]
  30. Rotman H. L., Schnyder-Candrian S., Scott P., Nolan T. J., Schad G. A., Abraham D. IL-12 eliminates the Th-2 dependent protective immune response of mice to larval Strongyloides stercoralis. Parasite Immunol. 1997 Jan;19(1):29–39. doi: 10.1046/j.1365-3024.1997.d01-142.x. [DOI] [PubMed] [Google Scholar]
  31. Rotman H. L., Yutanawiboonchai W., Brigandi R. A., Leon O., Gleich G. J., Nolan T. J., Schad G. A., Abraham D. Strongyloides stercoralis: eosinophil-dependent immune-mediated killing of third stage larvae in BALB/cByJ mice. Exp Parasitol. 1996 Apr;82(3):267–278. doi: 10.1006/expr.1996.0034. [DOI] [PubMed] [Google Scholar]
  32. Sanderson C. J. Interleukin-5, eosinophils, and disease. Blood. 1992 Jun 15;79(12):3101–3109. [PubMed] [Google Scholar]
  33. Sasaki O., Sugaya H., Ishida K., Yoshimura K. Ablation of eosinophils with anti-IL-5 antibody enhances the survival of intracranial worms of Angiostrongylus cantonensis in the mouse. Parasite Immunol. 1993 Jun;15(6):349–354. doi: 10.1111/j.1365-3024.1993.tb00619.x. [DOI] [PubMed] [Google Scholar]
  34. Sher A., Coffman R. L., Hieny S., Cheever A. W. 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. J Immunol. 1990 Dec 1;145(11):3911–3916. [PubMed] [Google Scholar]
  35. Sturrock R. F., Kimani R., Cottrell B. J., Butterworth A. E., Seitz H. M., Siongok T. K., Houba V. Observations on possible immunity to reinfection among Kenyan schoolchildren after treatment for Schistosoma mansoni. Trans R Soc Trop Med Hyg. 1983;77(3):363–371. doi: 10.1016/0035-9203(83)90166-9. [DOI] [PubMed] [Google Scholar]
  36. Sugaya H., Aoki M., Yoshida T., Takatsu K., Yoshimura K. Eosinophilia and intracranial worm recovery in interleukin-5 transgenic and interleukin-5 receptor alpha chain-knockout mice infected with Angiostrongylus cantonensis. Parasitol Res. 1997;83(6):583–590. doi: 10.1007/s004360050302. [DOI] [PubMed] [Google Scholar]
  37. Takamoto M., Ovington K. S., Behm C. A., Sugane K., Young I. G., Matthaei K. I. Eosinophilia, parasite burden and lung damage in Toxocara canis infection in C57Bl/6 mice genetically deficient in IL-5. Immunology. 1997 Apr;90(4):511–517. doi: 10.1046/j.1365-2567.1997.00208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Urban J. F., Jr, Katona I. M., Paul W. E., Finkelman F. D. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5513–5517. doi: 10.1073/pnas.88.13.5513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. WERTHEIM G., LENGY J. THE SEASONAL OCCURRENCE OF STRONGYLOIDES RATTI SANDGROUND, 1925 AND OF S. VENEZUELENSIS BRUMPT, 1934 IN A POPULATION OF RATTUS NORVEGICUS. J Helminthol. 1964;38:393–398. doi: 10.1017/s0022149x00033940. [DOI] [PubMed] [Google Scholar]
  40. Yamaguchi Y., Matsui T., Kasahara T., Etoh S., Tominaga A., Takatsu K., Miura Y., Suda T. In vivo changes of hemopoietic progenitors and the expression of the interleukin 5 gene in eosinophilic mice infected with Toxocara canis. Exp Hematol. 1990 Dec;18(11):1152–1157. [PubMed] [Google Scholar]
  41. Yoshida T., Ikuta K., Sugaya H., Maki K., Takagi M., Kanazawa H., Sunaga S., Kinashi T., Yoshimura K., Miyazaki J. Defective B-1 cell development and impaired immunity against Angiostrongylus cantonensis in IL-5R alpha-deficient mice. Immunity. 1996 May;4(5):483–494. doi: 10.1016/s1074-7613(00)80414-8. [DOI] [PubMed] [Google Scholar]

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