Skip to main content
NCBI home page
Gut logoLink to Gut
. 1996 Mar;38(3):328–336. doi: 10.1136/gut.38.3.328

Local entrapment of interferon gamma in the recovery from Shigella dysenteriae type 1 infection.

R Raqib 1, A Ljungdahl 1, A A Lindberg 1, U Andersson 1, J Andersson 1
PMCID: PMC1383059  PMID: 8675083

Abstract

In healthy controls (n = 8) living in shigella endemic areas, accumulation of interferon gamma (IFN gamma) in the epithelial lining was seen in the rectal tissues. At the single cell level, however, few or no IFN gamma protein producing cells or mRNA expressing cells were detected at that site indicating the involvement of the whole large intestine in the production of IFN gamma in controls. Persistent numbers of IFN gamma producing cells were detected in the rectum of patients with Shigella dysenteriae type 1 infection (n = 8) throughout the course of disease with a tendency to increase in the convalescent stage. A significantly increased extra cellular deposition of secreted IFN gamma in tissue was seen in convalescence when compared with the acute stage (p < 0.05). In addition, enzyme immunoassay showed increased stool concentration of IFN gamma in patients at the convalescent stage as well as in healthy controls. In situ hybridisation confirmed the results by showing increased frequency of IFN gamma mRNA containing cells at the late stage of the disease (p < 0.05). Extensive message for IFN gamma was evident in cells in the lamina propria with no detectable transcripts in the surface epithelium. A colocalisation of IFN gamma with the IFN gamma receptor expression, predominantly found in the epithelial lining was detected by immunohistochemistry. Semiquantitative evaluation by computerised image analysis showed a gradual increased expression of IFN gamma and its corresponding receptor in the convalescent stage of shigellosis. This suggested progressive entrapment and binding of IFN gamma to its specific receptor at the local site. The enhanced surface expression of IFN gamma receptor evident at the convalescent stage of shigellosis was comparable to the constitutive level of expression in the healthy subjects. Thus, immunity to shigellosis correlated to up-regulation of IFN gamma production and expression of IFN gamma receptor.

Full text

PDF
328

Images in this article

332Figure 1
on p.332
333Figure 2
on p.333

Selected References

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

  1. Andersson J., Nagy S., Björk L., Abrams J., Holm S., Andersson U. Bacterial toxin-induced cytokine production studied at the single-cell level. Immunol Rev. 1992 Jun;127:69–96. doi: 10.1111/j.1600-065x.1992.tb01409.x. [DOI] [PubMed] [Google Scholar]
  2. Björk L., Andersson U., Chauvet J. M., Skansén-Saphir U., Andersson J. Quantification of superantigen induced IFN-gamma production by computerised image analysis--inhibition of cytokine production and blast transformation by pooled human IgG. J Immunol Methods. 1994 Oct 14;175(2):201–213. doi: 10.1016/0022-1759(94)90363-8. [DOI] [PubMed] [Google Scholar]
  3. Bout D., Deslèe D., Capron A. Antischistosomal effect of cyclosporin A: cure and prevention of mouse and rat schistosomiasis mansoni. Infect Immun. 1986 Jun;52(3):823–827. doi: 10.1128/iai.52.3.823-827.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Celada A., Schreiber R. D. Internalization and degradation of receptor-bound interferon-gamma by murine macrophages. Demonstration of receptor recycling. J Immunol. 1987 Jul 1;139(1):147–153. [PubMed] [Google Scholar]
  5. Colgan S. P., Parkos C. A., Delp C., Arnaout M. A., Madara J. L. Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion. J Cell Biol. 1993 Feb;120(3):785–798. doi: 10.1083/jcb.120.3.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dagerlind A., Friberg K., Bean A. J., Hökfelt T. Sensitive mRNA detection using unfixed tissue: combined radioactive and non-radioactive in situ hybridization histochemistry. Histochemistry. 1992 Aug;98(1):39–49. doi: 10.1007/BF00716936. [DOI] [PubMed] [Google Scholar]
  7. Degré M., Bukholm G., Czarniecki C. W. In vitro treatment of HEp-2 cells with human tumor necrosis factor-alpha and human interferons reduces invasiveness of Salmonella typhimurium. J Biol Regul Homeost Agents. 1989 Jan-Mar;3(1):1–7. [PubMed] [Google Scholar]
  8. Dinarello C. A. Interleukin-1 and interleukin-1 antagonism. Blood. 1991 Apr 15;77(8):1627–1652. [PubMed] [Google Scholar]
  9. Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
  10. Dolhain R. J., Andersson U., ter Haar N. T., Brinkman B. M., Verweij C. L., Daha M. R., Breedveld F. C., Miltenburg A. M. Detection of intracellular interferon-gamma by light microscopy using an immunoperoxidase technique: correlation with the corresponding mRNA and protein product. J Leukoc Biol. 1993 Dec;54(6):545–551. doi: 10.1002/jlb.54.6.545. [DOI] [PubMed] [Google Scholar]
  11. Donta S. T., Tomicic T. K., Donohue-Rolfe A. Inhibition of Shiga-like toxins by brefeldin A. J Infect Dis. 1995 Mar;171(3):721–724. doi: 10.1093/infdis/171.3.721. [DOI] [PubMed] [Google Scholar]
  12. Gray P. W., Leung D. W., Pennica D., Yelverton E., Najarian R., Simonsen C. C., Derynck R., Sherwood P. J., Wallace D. M., Berger S. L. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
  13. Hernandez-Pando R., Rook G. A. The role of TNF-alpha in T-cell-mediated inflammation depends on the Th1/Th2 cytokine balance. Immunology. 1994 Aug;82(4):591–595. [PMC free article] [PubMed] [Google Scholar]
  14. Islam D., Wretlind B., Ryd M., Lindberg A. A., Christensson B. Immunoglobulin subclass distribution and dynamics of Shigella-specific antibody responses in serum and stool samples in shigellosis. Infect Immun. 1995 May;63(5):2054–2061. doi: 10.1128/iai.63.5.2054-2061.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kaldy P., Schmitt-Verhulst A. M. Regulation of interferon-gamma mRNA in a cytolytic T cell clone: Ca(2+)-induced transcription followed by mRNA stabilization through activation of protein kinase C or increase in cAMP. Eur J Immunol. 1995 Apr;25(4):889–895. doi: 10.1002/eji.1830250405. [DOI] [PubMed] [Google Scholar]
  16. Kaspar R. L., Gehrke L. Peripheral blood mononuclear cells stimulated with C5a or lipopolysaccharide to synthesize equivalent levels of IL-1 beta mRNA show unequal IL-1 beta protein accumulation but similar polyribosome profiles. J Immunol. 1994 Jul 1;153(1):277–286. [PubMed] [Google Scholar]
  17. Keusch G. T., Jacewicz M., Mobassaleh M., Donohue-Rolfe A. Shiga toxin: intestinal cell receptors and pathophysiology of enterotoxic effects. Rev Infect Dis. 1991 Mar-Apr;13 (Suppl 4):S304–S310. doi: 10.1093/clinids/13.supplement_4.s304. [DOI] [PubMed] [Google Scholar]
  18. Louise C. B., Obrig T. G. Shiga toxin-associated hemolytic-uremic syndrome: combined cytotoxic effects of Shiga toxin, interleukin-1 beta, and tumor necrosis factor alpha on human vascular endothelial cells in vitro. Infect Immun. 1991 Nov;59(11):4173–4179. doi: 10.1128/iai.59.11.4173-4179.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Madara J. L., Stafford J. Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest. 1989 Feb;83(2):724–727. doi: 10.1172/JCI113938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
  21. Perdomo J. J., Gounon P., Sansonetti P. J. Polymorphonuclear leukocyte transmigration promotes invasion of colonic epithelial monolayer by Shigella flexneri. J Clin Invest. 1994 Feb;93(2):633–643. doi: 10.1172/JCI117015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Perdomo O. J., Cavaillon J. M., Huerre M., Ohayon H., Gounon P., Sansonetti P. J. Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J Exp Med. 1994 Oct 1;180(4):1307–1319. doi: 10.1084/jem.180.4.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peyman J. A., Hammond G. L. Localization of IFN-gamma receptor in first trimester placenta to trophoblasts but lack of stimulation of HLA-DRA, -DRB, or invariant chain mRNA expression by IFN-gamma. J Immunol. 1992 Oct 15;149(8):2675–2680. [PubMed] [Google Scholar]
  24. Raqib R., Lindberg A. A., Wretlind B., Bardhan P. K., Andersson U., Andersson J. Persistence of local cytokine production in shigellosis in acute and convalescent stages. Infect Immun. 1995 Jan;63(1):289–296. doi: 10.1128/iai.63.1.289-296.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Raqib R., Wretlind B., Andersson J., Lindberg A. A. Cytokine secretion in acute shigellosis is correlated to disease activity and directed more to stool than to plasma. J Infect Dis. 1995 Feb;171(2):376–384. doi: 10.1093/infdis/171.2.376. [DOI] [PubMed] [Google Scholar]
  26. Redl H., Schlag G., Adolf G. R., Natmessnig B., Davies J. Tumor necrosis factor (TNF)-dependent shedding of the p55 TNF receptor in a baboon model of bacteremia. Infect Immun. 1995 Jan;63(1):297–300. doi: 10.1128/iai.63.1.297-300.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sartor R. B. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology. 1994 Feb;106(2):533–539. doi: 10.1016/0016-5085(94)90614-9. [DOI] [PubMed] [Google Scholar]
  28. Schindler R., Gelfand J. A., Dinarello C. A. Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. Blood. 1990 Oct 15;76(8):1631–1638. [PubMed] [Google Scholar]
  29. Tesh V. L., Ramegowda B., Samuel J. E. Purified Shiga-like toxins induce expression of proinflammatory cytokines from murine peritoneal macrophages. Infect Immun. 1994 Nov;62(11):5085–5094. doi: 10.1128/iai.62.11.5085-5094.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tesh V. L., Samuel J. E., Perera L. P., Sharefkin J. B., O'Brien A. D. Evaluation of the role of Shiga and Shiga-like toxins in mediating direct damage to human vascular endothelial cells. J Infect Dis. 1991 Aug;164(2):344–352. doi: 10.1093/infdis/164.2.344. [DOI] [PubMed] [Google Scholar]
  31. Valente G., Ozmen L., Novelli F., Geuna M., Palestro G., Forni G., Garotta G. Distribution of interferon-gamma receptor in human tissues. Eur J Immunol. 1992 Sep;22(9):2403–2412. doi: 10.1002/eji.1830220933. [DOI] [PubMed] [Google Scholar]
  32. Zychlinsky A., Fitting C., Cavaillon J. M., Sansonetti P. J. Interleukin 1 is released by murine macrophages during apoptosis induced by Shigella flexneri. J Clin Invest. 1994 Sep;94(3):1328–1332. doi: 10.1172/JCI117452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. van de Kar N. C., Monnens L. A., Karmali M. A., van Hinsbergh V. W. Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: implications for the pathogenesis of the hemolytic uremic syndrome. Blood. 1992 Dec 1;80(11):2755–2764. [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES