Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1995 Feb;63(2):681–685. doi: 10.1128/iai.63.2.681-685.1995

Inhibition of the Fc receptor-mediated oxidative burst in macrophages by the Yersinia pseudotuberculosis tyrosine phosphatase.

J B Bliska 1, D S Black 1
PMCID: PMC173049  PMID: 7822039

Abstract

Suppression of host-cell-mediated immunity is a hallmark feature of Yersinia pseudotuberculosis infection. To better understand this process, the interaction of Y. pseudotuberculosis with macrophages and the effect of the virulence plasmid-encoded Yersinia tyrosine phosphatase (YopH) on the oxidative burst was analyzed in a chemiluminescence assay. An oxidative burst was generated upon infection of macrophages with a plasmid-cured strain of Y. pseudotuberculosis opsonized with immunoglobulin G antibody. Infection with plasmid-containing Y. pseudotuberculosis inhibited the oxidative burst triggered by secondary infection with opsonized bacteria. The tyrosine phosphatase activity of YopH was necessary for this inhibition. These results indicate that YopH inhibits Fc receptor-mediated signal transduction in macrophages in a global fashion. In addition, bacterial protein synthesis was not required for macrophage inhibition, suggesting that YopH export and translocation are controlled at the posttranslational level.

Full Text

The Full Text of this article is available as a PDF (205.8 KB).

Selected References

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

  1. Bliska J. B., Clemens J. C., Dixon J. E., Falkow S. The Yersinia tyrosine phosphatase: specificity of a bacterial virulence determinant for phosphoproteins in the J774A.1 macrophage. J Exp Med. 1992 Dec 1;176(6):1625–1630. doi: 10.1084/jem.176.6.1625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bliska J. B., Copass M. C., Falkow S. The Yersinia pseudotuberculosis adhesin YadA mediates intimate bacterial attachment to and entry into HEp-2 cells. Infect Immun. 1993 Sep;61(9):3914–3921. doi: 10.1128/iai.61.9.3914-3921.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bliska J. B., Galán J. E., Falkow S. Signal transduction in the mammalian cell during bacterial attachment and entry. Cell. 1993 Jun 4;73(5):903–920. doi: 10.1016/0092-8674(93)90270-z. [DOI] [PubMed] [Google Scholar]
  4. Bliska J. B., Guan K. L., Dixon J. E., Falkow S. Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1187–1191. doi: 10.1073/pnas.88.4.1187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brubaker R. R. Factors promoting acute and chronic diseases caused by yersiniae. Clin Microbiol Rev. 1991 Jul;4(3):309–324. doi: 10.1128/cmr.4.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bölin I., Portnoy D. A., Wolf-Watz H. Expression of the temperature-inducible outer membrane proteins of yersiniae. Infect Immun. 1985 Apr;48(1):234–240. doi: 10.1128/iai.48.1.234-240.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bölin I., Wolf-Watz H. The plasmid-encoded Yop2b protein of Yersinia pseudotuberculosis is a virulence determinant regulated by calcium and temperature at the level of transcription. Mol Microbiol. 1988 Mar;2(2):237–245. doi: 10.1111/j.1365-2958.1988.tb00025.x. [DOI] [PubMed] [Google Scholar]
  8. CAVANAUGH D. C., RANDALL R. The role of multiplication of Pasteurella pestis in mononuclear phagocytes in the pathogenesis of flea-borne plague. J Immunol. 1959 Oct;83:348–363. [PubMed] [Google Scholar]
  9. China B., N'Guyen B. T., de Bruyere M., Cornelis G. R. Role of YadA in resistance of Yersinia enterocolitica to phagocytosis by human polymorphonuclear leukocytes. Infect Immun. 1994 Apr;62(4):1275–1281. doi: 10.1128/iai.62.4.1275-1281.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clemens J. C., Guan K., Bliska J. B., Falkow S., Dixon J. E. Microbial pathogenesis and tyrosine dephosphorylation: surprising 'bedfellows'. Mol Microbiol. 1991 Nov;5(11):2617–2620. doi: 10.1111/j.1365-2958.1991.tb01970.x. [DOI] [PubMed] [Google Scholar]
  11. Easmon C. S., Cole P. J., Williams A. J., Hastings M. The measurement of opsonic and phagocytic function by Luminol-dependent chemiluminescence. Immunology. 1980 Sep;41(1):67–74. [PMC free article] [PubMed] [Google Scholar]
  12. Falkow S., Isberg R. R., Portnoy D. A. The interaction of bacteria with mammalian cells. Annu Rev Cell Biol. 1992;8:333–363. doi: 10.1146/annurev.cb.08.110192.002001. [DOI] [PubMed] [Google Scholar]
  13. Forsberg A., Bölin I., Norlander L., Wolf-Watz H. Molecular cloning and expression of calcium-regulated, plasmid-coded proteins of Y. pseudotuberculosis. Microb Pathog. 1987 Feb;2(2):123–137. doi: 10.1016/0882-4010(87)90104-5. [DOI] [PubMed] [Google Scholar]
  14. Forsberg A., Rosqvist R., Wolf-Watz H. Regulation and polarized transfer of the Yersinia outer proteins (Yops) involved in antiphagocytosis. Trends Microbiol. 1994 Jan;2(1):14–19. doi: 10.1016/0966-842x(94)90339-5. [DOI] [PubMed] [Google Scholar]
  15. Fürste J. P., Pansegrau W., Frank R., Blöcker H., Scholz P., Bagdasarian M., Lanka E. Molecular cloning of the plasmid RP4 primase region in a multi-host-range tacP expression vector. Gene. 1986;48(1):119–131. doi: 10.1016/0378-1119(86)90358-6. [DOI] [PubMed] [Google Scholar]
  16. Gemski P., Lazere J. R., Casey T., Wohlhieter J. A. Presence of a virulence-associated plasmid in Yersinia pseudotuberculosis. Infect Immun. 1980 Jun;28(3):1044–1047. doi: 10.1128/iai.28.3.1044-1047.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ginocchio C. C., Olmsted S. B., Wells C. L., Galán J. E. Contact with epithelial cells induces the formation of surface appendages on Salmonella typhimurium. Cell. 1994 Feb 25;76(4):717–724. doi: 10.1016/0092-8674(94)90510-x. [DOI] [PubMed] [Google Scholar]
  18. Goguen J. D., Walker W. S., Hatch T. P., Yother J. Plasmid-determined cytotoxicity in Yersinia pestis and Yersinia pseudotuberculosis. Infect Immun. 1986 Mar;51(3):788–794. doi: 10.1128/iai.51.3.788-794.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Greenberg S., Chang P., Silverstein S. C. Tyrosine phosphorylation of the gamma subunit of Fc gamma receptors, p72syk, and paxillin during Fc receptor-mediated phagocytosis in macrophages. J Biol Chem. 1994 Feb 4;269(5):3897–3902. [PubMed] [Google Scholar]
  20. Guan K. L., Dixon J. E. Protein tyrosine phosphatase activity of an essential virulence determinant in Yersinia. Science. 1990 Aug 3;249(4968):553–556. doi: 10.1126/science.2166336. [DOI] [PubMed] [Google Scholar]
  21. Hale T. L., Oaks E. V., Formal S. B. Identification and antigenic characterization of virulence-associated, plasmid-coded proteins of Shigella spp. and enteroinvasive Escherichia coli. Infect Immun. 1985 Dec;50(3):620–629. doi: 10.1128/iai.50.3.620-629.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hanski C., Kutschka U., Schmoranzer H. P., Naumann M., Stallmach A., Hahn H., Menge H., Riecken E. O. Immunohistochemical and electron microscopic study of interaction of Yersinia enterocolitica serotype O8 with intestinal mucosa during experimental enteritis. Infect Immun. 1989 Mar;57(3):673–678. doi: 10.1128/iai.57.3.673-678.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hartland E. L., Green S. P., Phillips W. A., Robins-Browne R. M. Essential role of YopD in inhibition of the respiratory burst of macrophages by Yersinia enterocolitica. Infect Immun. 1994 Oct;62(10):4445–4453. doi: 10.1128/iai.62.10.4445-4453.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Heesemann J., Gross U., Schmidt N., Laufs R. Immunochemical analysis of plasmid-encoded proteins released by enteropathogenic Yersinia sp. grown in calcium-deficient media. Infect Immun. 1986 Nov;54(2):561–567. doi: 10.1128/iai.54.2.561-567.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. High N., Mounier J., Prévost M. C., Sansonetti P. J. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 1992 May;11(5):1991–1999. doi: 10.1002/j.1460-2075.1992.tb05253.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Horwitz M. A. Phagocytosis of the Legionnaires' disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil. Cell. 1984 Jan;36(1):27–33. doi: 10.1016/0092-8674(84)90070-9. [DOI] [PubMed] [Google Scholar]
  27. Isberg R. R. Determinants for thermoinducible cell binding and plasmid-encoded cellular penetration detected in the absence of the Yersinia pseudotuberculosis invasin protein. Infect Immun. 1989 Jul;57(7):1998–2005. doi: 10.1128/iai.57.7.1998-2005.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Isberg R. R., Swain A., Falkow S. Analysis of expression and thermoregulation of the Yersinia pseudotuberculosis inv gene with hybrid proteins. Infect Immun. 1988 Aug;56(8):2133–2138. doi: 10.1128/iai.56.8.2133-2138.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Isberg R. R., Tran Van Nhieu G. Binding and internalization of microorganisms by integrin receptors. Trends Microbiol. 1994 Jan;2(1):10–14. doi: 10.1016/0966-842x(94)90338-7. [DOI] [PubMed] [Google Scholar]
  30. Leong J. M., Fournier R. S., Isberg R. R. Mapping and topographic localization of epitopes of the Yersinia pseudotuberculosis invasin protein. Infect Immun. 1991 Oct;59(10):3424–3433. doi: 10.1128/iai.59.10.3424-3433.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lian C. J., Hwang W. S., Pai C. H. Plasmid-mediated resistance to phagocytosis in Yersinia enterocolitica. Infect Immun. 1987 May;55(5):1176–1183. doi: 10.1128/iai.55.5.1176-1183.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lian C. J., Pai C. H. Inhibition of human neutrophil chemiluminescence by plasmid-mediated outer membrane proteins of Yersinia enterocolitica. Infect Immun. 1985 Jul;49(1):145–151. doi: 10.1128/iai.49.1.145-151.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. MacBeth K. J., Lee C. A. Prolonged inhibition of bacterial protein synthesis abolishes Salmonella invasion. Infect Immun. 1993 Apr;61(4):1544–1546. doi: 10.1128/iai.61.4.1544-1546.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Miller V. L., Mekalanos J. J. A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR. J Bacteriol. 1988 Jun;170(6):2575–2583. doi: 10.1128/jb.170.6.2575-2583.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Payne N. R., Horwitz M. A. Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors. J Exp Med. 1987 Nov 1;166(5):1377–1389. doi: 10.1084/jem.166.5.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pepe J. C., Miller V. L. Yersinia enterocolitica invasin: a primary role in the initiation of infection. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6473–6477. doi: 10.1073/pnas.90.14.6473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pierson D. E., Falkow S. The ail gene of Yersinia enterocolitica has a role in the ability of the organism to survive serum killing. Infect Immun. 1993 May;61(5):1846–1852. doi: 10.1128/iai.61.5.1846-1852.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Portnoy D. A., Martinez R. J. Role of a plasmid in the pathogenicity of Yersinia species. Curr Top Microbiol Immunol. 1985;118:29–51. doi: 10.1007/978-3-642-70586-1_3. [DOI] [PubMed] [Google Scholar]
  39. Portnoy D. A., Wolf-Watz H., Bolin I., Beeder A. B., Falkow S. Characterization of common virulence plasmids in Yersinia species and their role in the expression of outer membrane proteins. Infect Immun. 1984 Jan;43(1):108–114. doi: 10.1128/iai.43.1.108-114.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rosqvist R., Bölin I., Wolf-Watz H. Inhibition of phagocytosis in Yersinia pseudotuberculosis: a virulence plasmid-encoded ability involving the Yop2b protein. Infect Immun. 1988 Aug;56(8):2139–2143. doi: 10.1128/iai.56.8.2139-2143.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rosqvist R., Forsberg A., Rimpiläinen M., Bergman T., Wolf-Watz H. The cytotoxic protein YopE of Yersinia obstructs the primary host defence. Mol Microbiol. 1990 Apr;4(4):657–667. doi: 10.1111/j.1365-2958.1990.tb00635.x. [DOI] [PubMed] [Google Scholar]
  42. Schlesinger L. S., Bellinger-Kawahara C. G., Payne N. R., Horwitz M. A. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol. 1990 Apr 1;144(7):2771–2780. [PubMed] [Google Scholar]
  43. Simonet M., Falkow S. Invasin expression in Yersinia pseudotuberculosis. Infect Immun. 1992 Oct;60(10):4414–4417. doi: 10.1128/iai.60.10.4414-4417.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Simonet M., Fortineau N., Beretti J. L., Berche P. Immunization with live aroA recombinant Salmonella typhimurium producing invasin inhibits intestinal translocation of Yersinia pseudotuberculosis. Infect Immun. 1994 Mar;62(3):863–867. doi: 10.1128/iai.62.3.863-867.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Straley S. C., Skrzypek E., Plano G. V., Bliska J. B. Yops of Yersinia spp. pathogenic for humans. Infect Immun. 1993 Aug;61(8):3105–3110. doi: 10.1128/iai.61.8.3105-3110.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tabor S., Richardson C. C. A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1074–1078. doi: 10.1073/pnas.82.4.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Tertti R., Eerola E., Lehtonen O. P., Ståhlberg T. H., Viander M., Toivanen A. Virulence-plasmid is associated with the inhibition of opsonization in Yersinia enterocolitica and Yersinia pseudotuberculosis. Clin Exp Immunol. 1987 May;68(2):266–274. [PMC free article] [PubMed] [Google Scholar]
  48. Zychlinsky A., Kenny B., Ménard R., Prévost M. C., Holland I. B., Sansonetti P. J. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol Microbiol. 1994 Feb;11(4):619–627. doi: 10.1111/j.1365-2958.1994.tb00341.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES