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Volume 47, Issue 2

Studies of persistent infection by serovar K in TPA-differentiated U937 cells and the role of IFN- Free

Abstract

Inoculation of phorbol ester-differentiated U937 cells as a model for human macrophages with of the urogenital serovar K resulted in a persistent infection, with maximal growth at day 7, until day 10 post-infection. At these times inclusion bodies were present in 0.5–2% of the cells. Typical inclusion bodies containing elementary bodies and reticulate bodies were observed by electron microscopy. Furthermore, single chlamydial particles resembling atypical elementary or intermediate bodies were identified in the cytoplasm in > 80% of the host cells. IFN- exerts antichlamydial activity in epithelial and fibroblastoid cells, but the infection of U937 cells by was not affected by IFN-. The activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) was not detected in untreated or in IFN--treated or chlamydiae-infected or mock-infected U937 cells. The presence of atypical persisting chlamydiae and the lack of IDO expression in U937 cells indicates that the development of these atypical bacteria is independent from IFN--mediated tryptophan deprivation and other IFN--mediated effects. Evaluation of persistently infected cells revealed that the expression of the chlamydial major outer-membrane protein, heat-shock protein (hsp60) and lipopolysaccharide (LPS) antigens was not significantly altered in the course of the culture. An intense staining of the LPS on the surface of the host cells was demonstrated by immunofluorescence. The data show that phorbol ester-differentiated U937 cells restrict chlamydial growth strongly but not completely through a mechanismxd distinct from IDO-mediated tryptophan deprivation. The mechanisms of persistence of chlamydiae in monocytes, which differ considerably from those described for other cells, require further investigation.

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© 1998 The Pathological Society of Great Britain and Ireland
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1998-02-01
2024-04-19
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References

  1. Ladany S., Sarov I. Recent advances in Chlamydia trachomatis. Eur J Epidemiol 1985; 1:235–256
     [Google Scholar]
  2. Schachter J. Chlamydial infections. West J Med 1990; 153:523–534
     [Google Scholar]
  3. Ward M., Bailey R., Lesley A., Kajbaf M., Robertson J., Mabey D. Persisting inapparent chlamydial infection in a trachoma endemic community in the Gambia. Scand J Infect Dis 1990 Suppl 69137–148
     [Google Scholar]
  4. Campbell L. A., Patton D. L., Moore D. E., Cappuccio A. L., Mueller B. A., Wang S. P. Detection of Chlamydia trachomatis deoxyribonucleic acid in women with tubal infertility. Fertil Steril 1993; 59:49–50
     [Google Scholar]
  5. Keat A., Dixey J., Sonnex C., Thomas B., Osborn M., Taylor-Robinson D. Chlamydia trachomatis and reactive arthritis: the missing link. Lancet 1987; 1:72–74
     [Google Scholar]
  6. Wollenhaupt J., Zeidler H. Chlamydia-induced arthritis. EULAR Bulletin 1990; 3:72–77
     [Google Scholar]
  7. Holland S. M., Hudson A. P., Bobo L. Demonstration of chlamydial RNA and DNA during a culture-negative state. Infect Immun 1992; 60:2040–2047
     [Google Scholar]
  8. Nanagara R., Li F., Beutler A., Hudson A., Schumacher H. R. Alteration of Chlamydia trachomatis biologic behavior in synovial membranes. Arthritis Rheum 1995; 38:1410–1417
     [Google Scholar]
  9. Schachter J., Moncada J., Dawson C. R. Nonculture methods for diagnosing chlamydial infection in patients with trachoma: a clue to pathogenesis of the disease?. J Infect Dis 1988; 158:1347–1352
     [Google Scholar]
  10. Mascia M. T., Manzini C. U., Manzini E. Chlamydia-induced arthritis. Immunofluorescent antibody studies of the synovial fluid from 4 patients. Clin Exp Rheumatol 1992; 10:425–426
     [Google Scholar]
  11. Taylor-Robinson D., Gilroy C. B., Thomas B. J., Keat A. C. S. Detection of Chlamydia trachomatis DNA in joints of reactive arthritis patients by polymerase chain reaction. Lancet 1992; 340:81–82
     [Google Scholar]
  12. Hammer M., Nettelnbreker E., Hopf S., Schmitz E., Porschke K., Zeidler H. Chlamydial rRNA in the joints of patients with Chlamydia-induced arthritis and undifferentiated arthritis. Clin Exp Rheumatol 1992; 10:63–66
     [Google Scholar]
  13. Schmitz E., Nettelnbreker E., Zeidler H., Hammer M., Manor E., Wollenhaupt J. Intracellular persistence of chlamydial major outer-membrane protein, lipopolysaccharide and ribosomal RNA after non-productive infection of human monocytes with Chlamydia trachomatis serovar K. J Med Microbiol 1993; 38:278–285
     [Google Scholar]
  14. Ishikawa H., Ohno O., Yamasaki K., Ikuta S., Hirohata K. Arthritis presumably caused by Chlamydia in Reiter’s syndrome. Case report with electronmicroscopic studies. J Bone Joint Surg 1986; 68A:777–779
     [Google Scholar]
  15. Koehler L., Nettelnbreker E., Ott N., Drommer W., Zeidler H. Persistent, non-productive infection of human peripheral blood monocytes with C. trachomatis is due to an intracellular growth arrest at an early stage of the chlamydial development. In Orfila J., Byrne G., Chemesky H. (eds) Chlamydial infections Societa Edirice Esculapio; Bolognia: 1994427–430
     [Google Scholar]
  16. Koehler L., Nettelnbreker E., Hudson A. P. Ultrastructural and molecular analyses of the persistence of Chlamydia trachomatis (serovar K) in human monocytes. Microb Pathog 1997; 22:133–142
     [Google Scholar]
  17. Hass R., Bartels H., Topley N. TPA-induced differentiation and adhesion of U937 cells: changes in ultrastructure, cytoskeletal organization and expression of cell surface antigens. Eur J Cell Biol 1989; 48:282–293
     [Google Scholar]
  18. Byrne G. I., Lahmann L. K., Landry G. J. Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect Immun 1986; 53:347–351
     [Google Scholar]
  19. Beatty W. L., Byrne G. I., Morrison R. P. Morphologic and antigenic characterization of interferon γ-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci USA 1993; 90:3998–4002
     [Google Scholar]
  20. Thomas S. M., Garrity L. F., Brandt C. R. IFN-gamma-mediated antimicrobial response. J Immunol 1993; 150:5529–5534
     [Google Scholar]
  21. Morrison R. P., Belland R. J., Lyng K., Caldwell H. D. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. J Exp Med 1989; 170:1271–1283
     [Google Scholar]
  22. Morrison R. P., Lyng K., Caldwell H. D. Chlamydial disease pathogenesis. Ocular hypersensitivity elicted by a genus-specific 57-kD protein. J Exp Med 1989; 169:663–675
     [Google Scholar]
  23. Caldwell H. D., Kromhout J., Schachter J. Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis. Infect Immun 1981; 31:1161–1176
     [Google Scholar]
  24. Daubener W., Wanagat N., Pilz K., Seghrouchni S., Fischer H. G., Hadding U. A new, simple, bioassay for human IFN-γ. J Immunol Methods 1994; 168:39–47
     [Google Scholar]
  25. Shemer Y., Sarov I. Inhibition of growth of Chlamydia trachomatis by human gamma interferon. Infect Immun 1985; 48:592–596
     [Google Scholar]
  26. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227:680–685
     [Google Scholar]
  27. Yuan Y., Lyng K., Zhang Y.-X., Rockey D. D., Morrison R. P. Monoclonal antibodies define genus-specific, species-specific, and cross-reactive epitopes of the chlamydial 60-kilodalton heat shock protein (hsp60): specific immunodetection and purification of chlamydial hsp60. Infect Immun 1992; 60:2288–2296
     [Google Scholar]
  28. Fu Y., Baumann M., Kosma P., Brade L., Brade H. A synthetic glycoconjugate representing the genus-specific epitope of chlamydial lipopolysaccharide exhibits the same specificity as its natural counterpart. Infect Immun 1992; 60:1314–1321
     [Google Scholar]
  29. Byrne G., Stephens R. S., Ada G. Workshop on in vitro neutralization of Chlamydia trachomatis: summary of proceedings. J Infect Dis 1993; 168:415–420
     [Google Scholar]
  30. Brade L., Nurminen P., Makela P., Brade H. Antigenic properties of Chlamydia trachomatis lipopolysaccharide. Infect Immun 1985; 48:569–572
     [Google Scholar]
  31. Brunham R. C., Peeling R., Maclean I., Kosseim M. L., Paraskevas M. Chlamydia trachomatis-associated ectopic pregnancy: serologic and histologic correlates. J Infect Dis 1992; 165:1076–1081
     [Google Scholar]
  32. Lee C. K., Moulder J. W. Persistent infection of mouse fibroblasts (McCoy cells) with a trachoma strain of Chlamydia trachomatis. Infect Immun 1981; 32:822–829
     [Google Scholar]
  33. Schumacher H. R., Magge S., Cherian P. V. Light and electron microscopic studies on the synovial membrane in Reiter’s syndrome. Immunocytochemical identification of chlamydial antigen in patients with early disease. Arthritis Rheum 1988; 31:937–946
     [Google Scholar]
  34. Manor E., Sarov I. Fate of Chlamydia trachomatis in human monocytes and monocyte-derived macrophages. Infect Immun 1986; 54:90–95
     [Google Scholar]
  35. Sarov I., Geron E., Shemer-Avni Y. Implications for persistent chlamydial infections of phagocyte-microorganism interplay. Eur J Microbiol Infect Dis 1991; 10:119–129
     [Google Scholar]
  36. Rothermel C. D., Rubin B. Y., Murray H. W. γ-interferon is the factor in lymphokine that activates human macrophages to inhibit intracellular Chlamydia psittaci replication. J Immunol 1983; 131:2542–2544
     [Google Scholar]
  37. Byrne G. Interferons, immunity and Chlamydiae. In Byrne G. I., Turco J. (eds) Interferon and nonviral pathogens New York: Marcel Dekker Inc; 198873–94
     [Google Scholar]
  38. Rapoza P., Tahija S. G., Carlin J. P., Miller S., Padilla M. P., Byrne G. I. Effect of interferon on a primary conjuctival epithelial cell model of trachoma. Invest Ophthalmol Vis Sci 1991; 32:2919–2923
     [Google Scholar]
  39. Beatty W. L., Belanger T. A., Desai A. A., Morrison R. P., Byrne G. I. Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence. Infect Immun 1994; 62:3705–3711
     [Google Scholar]
  40. Nettelnbreker E., Bonk C., Zeidler H., Kohler L. IFN-γ mediated persistence of Chlamydia trachomatis serovar K is reversible with tryptophan in Hep-2 cells but not in monocytic THP-1 cells. In Stany A. (ed) Proceedings of the Third Meeting of the European Society for Chlamydia Research Società Edirice Esculapio; Bolognia: 199686
     [Google Scholar]
  41. Hass R., Lonnemann G., Männel D. Regulation of TNF-alpha, IL-1 and IL-6 synthesis in differentiating human monoblastoid leukemic U937 cells. Leuk Res 1991; 15:327–339
     [Google Scholar]
  42. Kiekenbeck M., Bange F.-C., Vogel U., Däubener W., Böttger E. C. Characteristics of interferon induced tryptophan metabolism in human macrophages in vitro. Immunobiology 1993; 189:178
     [Google Scholar]
  43. Beatty W. L., Morrison R. P., Byrne G. I. Immunoelectron-micro-scopic quantitation of differential levels of chlamydial proteins in a cell culture model of persistent Chlamydia trachomatis infection. Infect Immun 1994; 62:4059–4062
     [Google Scholar]
  44. Heam S. A., McNabb G. L. Immunoelectron microscopic localization of chlamydial lipopolysaccharide (LPS) in McCoy cells inoculated with Chlamydia trachomatis. J Histochem Cytochem 1991; 39:1067–1075
     [Google Scholar]
  45. Karimi S. T., Schloemer R. H., Wilde C. E. Accumulation of chlamydial lipopolysaccharide antigen in the plasma membranes of infected cells. Infect Immun 1989; 57:1780–1785
     [Google Scholar]
  46. Rothermel C. D., Schachter J., Lavrich P., Lipsitz E. C., Francus T. Chlamydia trachomatis-induced production of interleukin-1 by human monocytes. Infect Immun 1989; 57:2705–2711
     [Google Scholar]
  47. Ingalls R. R., Rice P. A., Qureshi N., Takayama K., Lin J. S., Golenbock D. T. The inflammatory cytokine response to Chlamydia trachomatis infection is endotoxin mediated. Infect Immun 1995; 63:3125–3130
     [Google Scholar]
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Studies of persistent infection by Chlamydia trachomatis serovar K in TPA-differentiated U937 cells and the role of IFN-γ
J. Med. Microbiol. 47, 141 (1998); https://doi.org/10.1099/00222615-47-2-141
/content/journal/jmm/10.1099/00222615-47-2-141
/content/journal/jmm/10.1099/00222615-47-2-141
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