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. 1997 Aug;65(8):3261–3266. doi: 10.1128/iai.65.8.3261-3266.1997

Infection with Salmonella typhimurium modulates the immune response to Schistosoma mansoni glutathione-S-transferase.

E E Comoy 1, C Vendeville 1, A Capron 1, G Thyphronitis 1
PMCID: PMC175461  PMID: 9234784

Abstract

Immune response polarization is controlled by several factors, including cytokines, antigen-presenting cells, antigen dose, and others. We have previously shown that adjuvants and live vectors play a critical role in polarization. Thus, immunization with the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28-GST) in aluminum hydroxide induced a type 2 cytokine profile and the production of immunoglobulin G1 (IgG1)- and IgE-specific antibodies. In contrast, mice infected with recombinant Salmonella typhimurium expressing Sm28-GST developed a type 1 cytokine profile and produced IgG2a-specific antibodies against Sm28-GST and Salmonella antigens. In this study, to determine if S. typhimurium not expressing Sm28-GST would still influence the type of the response against this antigen, we compared the profiles of the immune responses generated against Sm28-GST administered in alum in mice infected and not infected with S. typhimurium. Infected mice generated both IgG1 and IgG2a antibodies against Sm28-GST, while noninfected mice produced only IgG1 anti-Sm28-GST antibodies. Moreover, interleukin-4 (IL-4) mRNA expression in infected mice was near background levels, while gamma interferon (IFN-gamma) mRNA expression in coinfected mice was significantly higher than in mice immunized with Sm28-GST in alum only. However, after antigen-specific stimulation in vitro with Sm28-GST, levels of IL-4 and IFN-gamma cytokine production were similar in the two groups of mice. These results suggest that (i) the immune milieu produced during an infection may modify the response against an irrelevant antigen and (ii) isotype switching may be influenced by the cytokine environment of a bystander immune response, even though the specific antigen-driven cytokine production is not modified. Thus, the isotypic profile is not always an absolute reflection of the cytokines produced by antigen-specific Th cells.

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Selected References

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  1. Balloul J. M., Grzych J. M., Pierce R. J., Capron A. A purified 28,000 dalton protein from Schistosoma mansoni adult worms protects rats and mice against experimental schistosomiasis. J Immunol. 1987 May 15;138(10):3448–3453. [PubMed] [Google Scholar]
  2. Balloul J. M., Sondermeyer P., Dreyer D., Capron M., Grzych J. M., Pierce R. J., Carvallo D., Lecocq J. P., Capron A. Molecular cloning of a protective antigen of schistosomes. Nature. 1987 Mar 12;326(6109):149–153. doi: 10.1038/326149a0. [DOI] [PubMed] [Google Scholar]
  3. Coffman R. L., Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986 Feb 1;136(3):949–954. [PubMed] [Google Scholar]
  4. Comoy E. E., Capron A., Thyphronitis G. In vivo induction of type 1 and 2 immune responses against protein antigens. Int Immunol. 1997 Apr;9(4):523–531. doi: 10.1093/intimm/9.4.523. [DOI] [PubMed] [Google Scholar]
  5. Cox F. E., Liew F. Y. T-cell subsets and cytokines in parasitic infections. Immunol Today. 1992 Nov;13(11):445–448. doi: 10.1016/0167-5699(92)90072-F. [DOI] [PubMed] [Google Scholar]
  6. Curry A. J., Else K. J., Jones F., Bancroft A., Grencis R. K., Dunne D. W. Evidence that cytokine-mediated immune interactions induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris. J Exp Med. 1995 Feb 1;181(2):769–774. doi: 10.1084/jem.181.2.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Else K. J., Hültner L., Grencis R. K. Cellular immune responses to the murine nematode parasite Trichuris muris. II. Differential induction of TH-cell subsets in resistant versus susceptible mice. Immunology. 1992 Feb;75(2):232–237. [PMC free article] [PubMed] [Google Scholar]
  8. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freeman G. J., Boussiotis V. A., Anumanthan A., Bernstein G. M., Ke X. Y., Rennert P. D., Gray G. S., Gribben J. G., Nadler L. M. B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. Immunity. 1995 May;2(5):523–532. doi: 10.1016/1074-7613(95)90032-2. [DOI] [PubMed] [Google Scholar]
  10. Gajewski T. F., Fitch F. W. Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4245–4252. [PubMed] [Google Scholar]
  11. Gueirard P., Minoprio P., Guiso N. Intranasal inoculation of Bordetella bronchiseptica in mice induces long-lasting antibody and T-cell mediated immune responses. Scand J Immunol. 1996 Feb;43(2):181–192. doi: 10.1046/j.1365-3083.1996.d01-30.x. [DOI] [PubMed] [Google Scholar]
  12. Heinzel F. P., Sadick M. D., Holaday B. J., Coffman R. L., Locksley R. M. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. doi: 10.1084/jem.169.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
  14. Khan C. M., Villarreal-Ramos B., Pierce R. J., Riveau G., Demarco de Hormaeche R., McNeill H., Ali T., Fairweather N., Chatfield S., Capron A. Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11261–11265. doi: 10.1073/pnas.91.23.11261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. King C. L., Stupi R. J., Craighead N., June C. H., Thyphronitis G. CD28 activation promotes Th2 subset differentiation by human CD4+ cells. Eur J Immunol. 1995 Feb;25(2):587–595. doi: 10.1002/eji.1830250242. [DOI] [PubMed] [Google Scholar]
  16. Kullberg M. C., Pearce E. J., Hieny S. E., Sher A., Berzofsky J. A. Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen. J Immunol. 1992 May 15;148(10):3264–3270. [PubMed] [Google Scholar]
  17. Le Gros G., Ben-Sasson S. Z., Seder R., Finkelman F. D., Paul W. E. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med. 1990 Sep 1;172(3):921–929. doi: 10.1084/jem.172.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Liew F. Y., Li Y., Moss D., Parkinson C., Rogers M. V., Moncada S. Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages. Eur J Immunol. 1991 Dec;21(12):3009–3014. doi: 10.1002/eji.1830211216. [DOI] [PubMed] [Google Scholar]
  19. Mandler R., Finkelman F. D., Levine A. D., Snapper C. M. IL-4 induction of IgE class switching by lipopolysaccharide-activated murine B cells occurs predominantly through sequential switching. J Immunol. 1993 Jan 15;150(2):407–418. [PubMed] [Google Scholar]
  20. Mills F. C., Thyphronitis G., Finkelman F. D., Max E. E. Ig mu-epsilon isotype switch in IL-4-treated human B lymphoblastoid cells. Evidence for a sequential switch. J Immunol. 1992 Aug 1;149(3):1075–1085. [PubMed] [Google Scholar]
  21. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  22. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  23. Pfeiffer C., Murray J., Madri J., Bottomly K. Selective activation of Th1- and Th2-like cells in vivo--response to human collagen IV. Immunol Rev. 1991 Oct;123:65–84. doi: 10.1111/j.1600-065x.1991.tb00606.x. [DOI] [PubMed] [Google Scholar]
  24. Ramarathinam L., Niesel D. W., Klimpel G. R. Ity influences the production of IFN-gamma by murine splenocytes stimulated in vitro with Salmonella typhimurium. J Immunol. 1993 May 1;150(9):3965–3972. [PubMed] [Google Scholar]
  25. Schmitz J., Assenmacher M., Radbruch A. Regulation of T helper cell cytokine expression: functional dichotomy of antigen-presenting cells. Eur J Immunol. 1993 Jan;23(1):191–199. doi: 10.1002/eji.1830230130. [DOI] [PubMed] [Google Scholar]
  26. Scott P. IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. J Immunol. 1991 Nov 1;147(9):3149–3155. [PubMed] [Google Scholar]
  27. Seder R. A., Paul W. E. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994;12:635–673. doi: 10.1146/annurev.iy.12.040194.003223. [DOI] [PubMed] [Google Scholar]
  28. Sher A., Coffman R. L. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol. 1992;10:385–409. doi: 10.1146/annurev.iy.10.040192.002125. [DOI] [PubMed] [Google Scholar]
  29. Silva J. S., Morrissey P. J., Grabstein K. H., Mohler K. M., Anderson D., Reed S. G. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. J Exp Med. 1992 Jan 1;175(1):169–174. doi: 10.1084/jem.175.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
  31. Sornasse T., Larenas P. V., Davis K. A., de Vries J. E., Yssel H. Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level. J Exp Med. 1996 Aug 1;184(2):473–483. doi: 10.1084/jem.184.2.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Svetić A., Finkelman F. D., Jian Y. C., Dieffenbach C. W., Scott D. E., McCarthy K. F., Steinberg A. D., Gause W. C. Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody. J Immunol. 1991 Oct 1;147(7):2391–2397. [PubMed] [Google Scholar]
  33. Swain S. L. Generation and in vivo persistence of polarized Th1 and Th2 memory cells. Immunity. 1994 Oct;1(7):543–552. doi: 10.1016/1074-7613(94)90044-2. [DOI] [PubMed] [Google Scholar]
  34. Swain S. L., Weinberg A. D., English M., Huston G. IL-4 directs the development of Th2-like helper effectors. J Immunol. 1990 Dec 1;145(11):3796–3806. [PubMed] [Google Scholar]
  35. Szabo S. J., Jacobson N. G., Dighe A. S., Gubler U., Murphy K. M. Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity. 1995 Jun;2(6):665–675. doi: 10.1016/1074-7613(95)90011-x. [DOI] [PubMed] [Google Scholar]
  36. Taylor J. B., Vidal A., Torpier G., Meyer D. J., Roitsch C., Balloul J. M., Southan C., Sondermeyer P., Pemble S., Lecocq J. P. The glutathione transferase activity and tissue distribution of a cloned Mr28K protective antigen of Schistosoma mansoni. EMBO J. 1988 Feb;7(2):465–472. doi: 10.1002/j.1460-2075.1988.tb02834.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Thatte J., Rath S., Bal V. Immunization with live versus killed Salmonella typhimurium leads to the generation of an IFN-gamma-dominant versus an IL-4-dominant immune response. Int Immunol. 1993 Nov;5(11):1431–1436. doi: 10.1093/intimm/5.11.1431. [DOI] [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. Verwaerde C., Auriault C., Damonneville M., Neyrinck J. L., Vendeville C., Capron A. Role of serine proteases of Schistosoma mansoni in the regulation of IgE synthesis. Scand J Immunol. 1986 Nov;24(5):509–516. doi: 10.1111/j.1365-3083.1986.tb02165.x. [DOI] [PubMed] [Google Scholar]
  40. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]

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