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Immunomodulation by Mycoplasmas: Artifacts, Facts and Active Molecules

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Book cover Molecular Biology and Pathogenicity of Mycoplasmas

Abstract

One of the earliest reports on mycoplasma-mediated immunomodulation was a study concerning the toxicity of heat-killed mycoplasmas28. As is now known, bacterial toxicity, if not caused by exotoxins, is the result of excessive stimulation of the innate immune system through the so-called bacterial modulins; these are mostly components of the cell wall35 and, possibly, pieces of nucleic acids containing the motif CpG51. Cells of the innate immune system, in particular of the monocyte/macrophage lineage, react to these components by release of proinflammatory cytokines and IFN-γ, which in turn can lead to shock and death116. When the observations of Gabridge and Murphy28 were made, knowledge about these potent mediators of various cellular responses was nonexistent and the data were uninterpretable in modern terms. However, their report is a good example of a study which intentionally dealt with mycoplasmas. Many more studies were published, and some until quite recently, in which immunomodulation due to the presence of mycoplasmas was unknowingly observed and reported.

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References

  1. Allan, R. G., and Kwiatkowski, D., 1993, Plasmodium falciparum varies in its ability to induce tumor necrosis factor. Infect. Immun. 61:4772–4776

    PubMed Central  PubMed  CAS  Google Scholar 

  2. Atkin, C. L.; Cole, B. C; Sullivan, G. J.; Washburn, L. R., and Wiley, B. B., 1986, Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. V. A small basic protein from culture supernatants is a potent T cell mitogen. J. Immunol. 137:1581–1589

    PubMed  CAS  Google Scholar 

  3. Baeuerle, P. A., and Henkel, T., 1994, Function and activation of NF-kB in the immune system. Annu. Rev. Immunol. 12:141 – 179

    PubMed  CAS  Google Scholar 

  4. Beezholt, D. H.; Leftwich, J. A., and Hall, R. E., 1989, P48 induces tumor necrosis factor and IL-1 secretion by human monocytes. J. Immunol. 143:3217–3221

    Google Scholar 

  5. Bessler, W. G.; Cox, M.; Lex, A.; Suhr, B.; Wiesmüller, K. H., and Jung, G., 1985, Synthetic lipopeptide analogs of bacterial lipoprotein are potent polyclonal activators for murine B lymphocytes. J. Immunol. 135:1900–1905

    PubMed  CAS  Google Scholar 

  6. Biberfeld, G., and Nilsson, E., 1978, Mitogenicity of Mycoplasma fermentans for human lymphocytes. Infect. Immun. 21:48–54

    Google Scholar 

  7. Bogdan, C; Rollinghoff, M., and Diefenbach, A., 2000, The role of nitric oxide in innate immunity. Immunol. Rev. 173:17–26

    PubMed  CAS  Google Scholar 

  8. Bowie, A., and O’Neill, L. A., 2000, The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products. J. Leukoc. Biol. 67:508–514

    PubMed  CAS  Google Scholar 

  9. Brade, H.; Opal, S. M.; Vogel, S. N. und Morrison, D.C. eds., 1999, Endotoxin in health and disease. Marcel Dekker, New York.

    Google Scholar 

  10. Braun, V.; Wu, H. C., 1994, Lipoproteins, structure, function, biosynthesis and model for protein export. Bacterial cell wall. (Ghuysen, J.-M. und Hakenbeck, R .eds.), Elsevier Science„ pp. 319–341.

    Google Scholar 

  11. Bredt, W.; Wellek, B.; Brunner, H., and Loos, M., 1977, Interactions between Mycoplasma pneumoniae and the first component of complement. Infect. Immun. 15:7–12

    PubMed Central  PubMed  CAS  Google Scholar 

  12. Brenner, C; Wroblewski, H.; le Henaff, M.; Montagnier, L., and Blanchard, A., 1997, Spiralin, a mycoplasmal membrane lipoprotein, induces T-cell-independent B-cell blastogenesis and secretion of proinflammatory cytokines . Infect. Immun. 65:4322–4329

    PubMed Central  PubMed  CAS  Google Scholar 

  13. Brenner, T.; Yamin, A.; Abramsky, O., and Gallily, R., 1993, Stimulation of tumor necrosis factor-a production by mycoplasmas and inhibition by dexamethasone in cultured astrocytes. Brain Research 608:273–279

    PubMed  CAS  Google Scholar 

  14. Bricker, T. M.; Boyer, M. J.; Keith, J.; Watson-McKown, R., and Wise, K. S., 1988, Association of lipids with integral membrane surface membrane proteins of Mycoplasma hyorhinis. Infect. Immun. 56:295–301

    CAS  Google Scholar 

  15. Calcutt, M. J.; Kim, M. F.; Karpas, A. B.; Mühlradt, P. F., and Wise, K. S., 1999, Differential post-translational processing confers intraspecies variation of a major lipopeptide (MALP-2) of Mycoplasma fermentans. Infect. Immun. 67:760–771

    PubMed Central  PubMed  CAS  Google Scholar 

  16. Cario, E.; Rosenberg, I. M.; Brandwein, S. L.; Beck, P. L.; Reinecker, H. C., and Podolsky, D. K., 2000, Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J. Immunol. 164:966–972

    PubMed  CAS  Google Scholar 

  17. Chambaud, L; Wroblewski, H., and Blanchard, A., 1999, Interactions between mycoplasma lipoproteins and the host immune system. Trends in Microbiology 7:493–499

    PubMed  CAS  Google Scholar 

  18. Chelmonska-Soyta, A.; Miller, R. B., and Rosendal, S., 1994, Activation of murine macrophages and lymphocytes by Ureaplasma diversum. Can. J. Vet. Res. 58:275–280

    CAS  Google Scholar 

  19. Cifone, M. G.; Cironi, L.; Meccia, M. A.; Roncaioli, P.; Festuccia, C; De-Nuntiis, G.; Dálo, S., and Santoni, A., 1995, Role of nitric oxide in cell-mediated tumor cytotoxicity. Adv. Neuroimmunol. 5:443–461

    PubMed  CAS  Google Scholar 

  20. Cole, B. C., 1999, Mycoplasma-induced arthritis in animals: relevance to understanding the etiologies of the human rheumatic diseases. Rev. Rhum. Engl. Ed. 66(1 Suppl):45S–49S

    Google Scholar 

  21. Deiters, U., and Mühlradt, P. F., 1999, Mycoplasmal lipopeptide MALP-2 induces the chemoattractant proteins macrophage inflammatory protein 1a (MIP-1a), monocyte chemoattractant protein 1, and MIP-2 and promotes leukocyte infiltration in mice. Infect. Immun. 67:3390–3398

    PubMed Central  PubMed  CAS  Google Scholar 

  22. Dong, L.; Shibata, K.; Sawa, Y.; Hasebe, A.; Yamaoka, Y.; Yoshida, S., and Watanabe, T., 1999, Transcriptional activation of mRNA of intercellular adhesion molecule 1 and induction of its cell surface expression in normal human gingival fibroblasts by Mycoplasma salivarium and Mycoplasma fermentans. Infect. Immun. 67:3061–3065

    CAS  Google Scholar 

  23. Feng, S.-H., and Lo, S.-C., 1994, Induced mouse spleen B-cell proliferation and secretion of immunoglobulin by lipid-associated membrane proteins of Mycoplasma fermentans incognitus and Mycoplasma penetrans M. Infect. Immun. 62:3916–3921

    PubMed Central  PubMed  CAS  Google Scholar 

  24. Feng SH, and Lo SC, 1999, Lipid extract of Mycoplasma penetrans proteinase K-digested lipid-associated membrane proteins rapidly activates NF-kappaB and activator protein 1. Infect. Immun. 67:2951–2956

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Fidler, I. J.; Nu, A.; Utsugi, T.; Brown, D.; Bakouche, O., and Kleinerman, E. S., 1990, Differential release of TNF-α, IL 1, and PGE2 by human blood monocytes subsequent to interaction with different bacterial derived agents. Lymphokine Res. 9:449–463

    PubMed  CAS  Google Scholar 

  26. Freudenberg, M. A., and Galanos, C., 1985, Alterations in rats in vivo of the chemical structure of lipopolysaccharide from Salmonella equi. Eur. J. Biochem. 152:353–359

    PubMed  CAS  Google Scholar 

  27. Frisch, M.; Gradehandt, G., and Mühlradt, P. F., 1996, Mycoplasma fermentans-áeáveá lipid inhibits class II major histocompatibility complex expression without mediation by interleukin-6, interleukin-10, tumor necrosis factor, transforming growth factor-ß, type I interferon, prostaglandins or nitric oxide. Eur. J. Immunol. 26:1050–1057

    PubMed  CAS  Google Scholar 

  28. Gabridge, M. G., and Murphy, W. H., 1971, Toxic membrane fractions from Mycoplasma fermentans. Infect. Immun. 4:678–682

    CAS  Google Scholar 

  29. Galanos, C; Gumenscheimer, M.; Mühlradt, P. F.; Jirillo, E., and Freudenberg, M. A., 2001, MALP-2, a mycoplasma lipopeptide with classical endotoxic properties: end of an era of LPS monopoly ?. J. Endotoxin Res. 6:471–476

    Google Scholar 

  30. Gallily, R.; Kipper-Galperin, M., and Brenner, T., 1999, Mycoplasma fermentans-induced inflammatory response of astrocytes: selective modulation by aminoguanidine, thalidomide, pentoxifylline and IL-10. Inflammation 23:495–505

    PubMed  CAS  Google Scholar 

  31. Garcia, J.; Lemercier, B.; Roman-Roman, S., and Rawadi, G., 1998, A Mycoplasma fermentans -derived synthetic lipopeptide induces AP-1 and NF-kB activity and cytokine secretion in macrophages via the activation of mitogen-activated protein kinase pathway. J. Biol.Chem. 273:34391–34398

    PubMed  CAS  Google Scholar 

  32. Haier, J.; Nasralla, M.; Franco, A. R., and Nicolson, G. L., 1999, Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis. Rheumatology Oxford 38:504–509

    PubMed  CAS  Google Scholar 

  33. Hall, R. E.; Agarwal, S.; Kestler, D. P.; Cobb, J. A.; Goldstein, K. M., and Chang, N.-S., 1996, cDNA and genomic cloning and expression of the P48 monocytic differentiation/activation factor, a Mycoplasma fermentans gene product. Biochem. J. 319:919–927

    PubMed Central  PubMed  CAS  Google Scholar 

  34. Hauschildt, S.; Lückhoff, A.; Mülsch, A.; Kohler, J.; Bessler, W., and Busse, R., 1990, Induction and activity of NO synthase in bone-marrow -derived macrophages are independent of Ca++. Biochem. J. 270:351–356

    PubMed Central  PubMed  CAS  Google Scholar 

  35. Henderson, B.; Poole, S., and Wilson, M., 1996, Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis. Microbiol. Rev. 60:316–341

    PubMed Central  PubMed  CAS  Google Scholar 

  36. Herbelin, A.; Ruuth, E.; Delorme, D.; Michel-Herbelin, C., and Praz, F., 1994, Mycoplasma arginini TUH-14 membrane lipoproteins induce production of interleukin-1, interleukin-6, and tumor necrosis factor alpha by human monocytes. Infect. Immun. 62:4690–4694

    PubMed Central  PubMed  CAS  Google Scholar 

  37. Himmelreich, R.; Plagens, H.; Hilbert, H.; Reiner, B., and Herrman, R., 1997, Comparative analysis of the genomes of the bacteria Mycoplasma pneumoniae and Mycoplasma genitalium. Nucleic Acids Res. 25:701 – 712

    PubMed Central  PubMed  CAS  Google Scholar 

  38. Hirschfeld, M.; Kirschning, C. J.; Schwandner, R.; Wesche, H.; Weis, J. H.; Wooten, R. M., and Weis, J. J., 1999, Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J. Immunol. 163:2382–2386

    PubMed  CAS  Google Scholar 

  39. Hommel-Berrey, G. A., and Brahmi, Z., 1987, Relevance of soluble cytotoxic factors generated by mycoplasma-contaminated targets to natural killer cell-mediated killing. . Hum. Immunol. 20:33–46

    PubMed  CAS  Google Scholar 

  40. Hoshino, K.; Takeuchi, O.; Kawai, T.; Sanjo, H.; Ogawa, T.; Takeda, Y., and Akira, S., 1999, Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J. Immunol. 162:3749–3752

    PubMed  CAS  Google Scholar 

  41. Jan, G.; Fontenelle, C; Le Hénaff, M., and Wróblewski, H., 1995, Acylation and immunological properties of Mycoplasma gallisepticum membrane proteins. Res. Microbiol. 146:739–750

    PubMed  CAS  Google Scholar 

  42. Kaufmann, A.; Mühlradt, P. F.; Gemsa, D., and Sprenger, H., 1999, Induction of cytokines and chemokines in human monocytes by Mycoplasma fermentans-derived lipoprotein MALP-2. Infect. Immun. 67:6303–6308

    PubMed Central  PubMed  CAS  Google Scholar 

  43. Kirchner, H.; Brehm, G.; Nicklas, W.; Beck, R., and Herbst, F., 1986, Biochemical characterization of the T-cell mitogen derived from Mycoplasma arthritidis. Scand. J. Immunol. 24:245–249

    PubMed  CAS  Google Scholar 

  44. Kita, M.; Ohmoto, Y.; Hirai, Y.; Yamaguchi, N., and Imanishi, J., 1992, Induction of cytokines in human peripheral blood mononuclear cells by mycoplasmas. Microbiol. Immunol. 36:507–516

    PubMed  CAS  Google Scholar 

  45. Kostyal, D. A.; Butler, G. H., and Beezhold, D. H., 1994, A 48-kilodalton Mycoplasma fermentans membrane protein induces cytokine secretion by human monocytes. Infect. Immun. 62:3793–3800

    PubMed Central  PubMed  CAS  Google Scholar 

  46. Kruger, T., and Baier, J., 1997, Induction of neutrophil chemoattractant cytokines by Mycoplasma hominis in alveolar type II cells. Infect. Immun. 65:5131–5136

    PubMed Central  PubMed  CAS  Google Scholar 

  47. LeHennaff, M.; Guegen, M. M., and Fontenelle, C., 2000, Selective acylation of plasma membrane proteins of Mycoplasma agalactiae: the causal agent of agalactia. Curr. Microbiol. 40:23–28

    Google Scholar 

  48. Lien E; Sellati TJ; Yoshimura A; Flo TH; Rawadi G; Finberg RW; Carroll JD; Espevik T; Ingalls RR; Radolf JD, and Golenbock DT, 1999, Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J-Biol-Chem. 274:33419–33425

    PubMed  CAS  Google Scholar 

  49. Lincoln, C. K., and Gabridge, M. G., 1998, Cell culture contamination: sources, consequences, prevention, and elimination. Methods Cell Biol. 57:49–65

    PubMed  CAS  Google Scholar 

  50. Lindsey, J. R., and Cassell, G. H., 1973, Experimental Mycoplasma pulmonis infection in pathogen-free mice. Am. J. Pathol. 72:63–90

    PubMed Central  PubMed  CAS  Google Scholar 

  51. Liu, H. M.; Newbrough, S. E.; Bhatia, S. K.; Dahle, C. E.; Krieg, A. M., and Weiner, G. J., 1998, Immunostimulatory CpG oligodeoxynucleotides enhance the immune response to vaccine strategies involving granulocyte-macrophage colony-stimulating factor. Blood 92:3730–3736

    PubMed  CAS  Google Scholar 

  52. Loewenstein, J.; Rottem, S., and Gallily, R., 1983, Induction of macrophage-mediated cytolysis of neoplastic cells by mycoplasmas. Cellular Immunology 77:290–297

    PubMed  CAS  Google Scholar 

  53. Lopez, A.; Maxie, M. G.; Ruhnke, L.; Savan, M., and Thomson, R. G., 1986, Cellular inflammatory response in the lungs of calves exposed to bovine viral diarrhea virus, Mycoplasma bovis, and Pasteurella haemolytica . Am. J. Vet. Res. 47:1283–1286

    PubMed  CAS  Google Scholar 

  54. Marshall, A. J.; Miles, R. J., and Richards, L., 1995, The phagocytosis of mycoplasmas. J. Med. Microbiol. 43:239–250

    PubMed  CAS  Google Scholar 

  55. Matsuda, K.; Kasamara, T.; Ishizuka, I.; Handa, S.; Yamamoto, N., and Taki, T., 1994, Structure of a novel phosphocholine-containing glycoglycerolipid from Mycoplasma fermentans. J. Biol. Chem. 269:33123–33128

    PubMed  CAS  Google Scholar 

  56. Matsumoto, M.; Yamashita, F.; Iida, K.; Tomita, M., and Seya, T., 1995, Purification and characterization of a human membrane protein that activates the alternative complement pathway and allows the deposition of homologous complement C3. J. Exp. Med. 181:115–125

    PubMed  CAS  Google Scholar 

  57. Matsumoto, M.; Takeda, J.; Inoue, N.; Hara, T.; Hatanaka, M.; Takahashi, K.; Nagasawa, S.; Akedo, H., and Seya, T., 1997, A novel protein that participates in nonself discrimination of malignant cells by homologous complement. Nature Medicine 3:1266–1270

    PubMed  CAS  Google Scholar 

  58. Matsumoto, M.; Nishiguchi, M.; Kikkawa, S.; Nishimura, H.; Nagasawa, S., and Seya, T., 1998, Structural and functional properties of complement-activating protein M161Ag, a Mycoplasma fermentans gene product that induces cytokine production by human monocytes. J. Biol. Chem. 273:12407–12414

    PubMed  CAS  Google Scholar 

  59. May, M. J., and Ghosh, S., 1998, Signal transduction through NF-kappaB. Immunol, today 19:80–88

    CAS  Google Scholar 

  60. Melchers, F.; Braun, V., and Galanos, C., 1975, The lipoprotein of the outer membrane of Escherichia coli: a B-lymphocyte mitogen. J. Exp. Med. 142:473–482

    PubMed  CAS  Google Scholar 

  61. Metzger, J.; Wiesmüller, K.-H.; Schaude, R.; Bessler, W. G., and Jung, G., 1991, Synthesis and novel immunologically active tripalmitoyl-S-glycerylcysteinyl lipopeptides as useful intermediates for immunogen preparations. Int. J. Pept. Protein Res. 37:46–57

    PubMed  CAS  Google Scholar 

  62. Metzger, J. W.; Beck-Sickinger, A. G.; Loleit, M.; Bessler, M. E. W. G., and Jung, G., 1995, Synthetic S-(2,3-dihydroxypropyl)-cysteinyl peptides derived from the N-terminus of the cytochrome subunit of the photoreaction centre of Rhodopseudomonas viridis enhance murine splenocyte proliferation. J. Pept. Sci. 3:184–190

    Google Scholar 

  63. Miller, R. A., and Britigan, B. E., 1997, Role of oxidants in microbial pathophysiology. Clin. Microbiol. Rev. 10:1–18

    PubMed Central  PubMed  CAS  Google Scholar 

  64. Mühlradt, P. F., and Frisch, M., 1994, Purification and partial biochemical characterization of a Mycoplasma fermentans-derived substance that activates macrophages to release nitric oxide, tumor necrosis factor, and interleukin-6. Infect. Immun. 62:3801–3807

    PubMed Central  PubMed  Google Scholar 

  65. Mühlradt, P. F., and Schade, U., 1991, MDHM, a macrophage-stimulatory product of Mycoplasma fermentans, leads to in vitro interleukin-1 (IL-1), IL-6, tumor necrosis factor, and prostaglandin production and is pyrogenic in rabbits. Infect. Immun. 59:3969–3974

    PubMed Central  PubMed  Google Scholar 

  66. Mühlradt, P. F.; Quentmeier, H., and Schmitt, E., 1991, Involvement of interleukin-1 (IL-1), IL-6, IL-2, and IL-4 in generation of cytolytic T cells from thymocytes stimulated by a Mycoplasma fermentans-denved product. Infect. Immun. 59:3962–3968

    PubMed Central  PubMed  Google Scholar 

  67. Mühlradt, P. F.; Meyer, H., and Jansen, R., 1996, Identification of S-(2,3-dihydroxypropyl)cystein in a macrophage-activating lipopeptide from . Biochemistry 35:7781–7786

    PubMed  Google Scholar 

  68. Mühlradt, P. F.; Kiess, M.; Meyer, H.; Süssmuth, R., and Jung, G., 1997, Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at pico molar concentration. J. Exp. Med. 185:1951–1958

    PubMed Central  PubMed  Google Scholar 

  69. Mühlradt, P. F.; Kiess, M.; Meyer, H.; Süssmuth, R., and Jung, G., 1997, Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at pico molar concentration Mycoplasma fermentans. J. Exp. Med. 185:1951–1958

    PubMed Central  PubMed  Google Scholar 

  70. Muzio, M.; Polentarutti, N.; Bosisio, D.; Prahladan, M. K., and Mantovani, A., 2000, Toll-like receptors: a growing family of immune receptors that are differentially expressed and regulated by different leukocytes. J-Leukoc-Biol. 67:450–456

    PubMed  CAS  Google Scholar 

  71. Naot, Y.; Merchav, S., and Ginsburg, H., 1979, Mycoplasma neurolyticum: a potent mitogen for rat B lymphocytes. Eur. J. Immunol. 9:185–189

    PubMed  CAS  Google Scholar 

  72. Norgard, M. V.; Arndt, L. L.; Akins, D. A.; Curetty, L. L.; Harrich, D. A., and Radolf, J. D., 1996, Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a different pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kB. Infect. Immun. 64:3845–3852

    PubMed Central  PubMed  CAS  Google Scholar 

  73. Novak, J. F.; Hayes, J. D. J., and McMaster, J. H., 1995, Mycoplasma-mediated bone resorption in bone organ cultures. Microbios 81:241–260

    PubMed  CAS  Google Scholar 

  74. Nyström, S., and Wieslander, A., 1992, Isoprenoid modification of proteins distinct from membrane acyl proteins in the procaryote Acholeplasma laidlawii . Biochim. Biophys. Acta 1107:39–43

    PubMed  Google Scholar 

  75. Nyström, S.; Wallbrandt, P., and Wieslander, A., 1992, Membrane protein acylation. Preference for exogenous myristic acid or endogenous saturated chains in Acholeplasma laidlawii. Eur. J. Biochem. 204:231–240

    PubMed  Google Scholar 

  76. Piec, G.; Mirkovitch, J.; Palacio, S.; Mühlradt, P. F., and Felix, R., 1999, Effect of MALP-2, a lipopeptide from Mycoplasma fermentans, on bone resorption in vitro . Infect. Immun. 67:6281–6285

    PubMed Central  PubMed  CAS  Google Scholar 

  77. Poltorak, A.; He, X.; Smirnova, I.; Liu, M.-Y.; VanHuffel, C; Du, X.; Birdwell, D.; Alejos, E.; Silva, M.; Galanos, C; Freudenberg, M. R.-C. P.; Layton, B., and Beutler, B., 1998, Poltorak, A., X. He, I. Smirnova, M.-Y. Liu, C. V. Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, . M Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088

    PubMed  CAS  Google Scholar 

  78. Proust, J. J.; Buchholz, M. A., and Nordin, A. A., 1985, A “lymphokine-like” soluble product that induces proliferation and maturation of B cells appears in the serum-free supernatant of a T cell hybridoma as a consequence of mycoplasmal contamination. J. Immunol. 134:390–396

    PubMed  CAS  Google Scholar 

  79. Quentmeier, H.; Schmitt, E.; Kirchhoff, H.; Grote, W., and Mühlradt, P. F., 1990, Mycoplasma fermentans-derived high molecular weight material induces interleukin-6 release in cultures of murine macrophages and human monocytes. Infect. Immun. 58:1273–1280

    PubMed Central  PubMed  CAS  Google Scholar 

  80. Quentmeier, H.; Klaucke, J.; Mühlradt, P. F., and Drexler, H. G., 1992, Role of IL-6, IL-2, and IL-4 in the in vitro induction of cytotoxic T cells. J. Immunol. 149:3316–3320

    PubMed  CAS  Google Scholar 

  81. Radolf, J. D.; Arndt, L. L.; Akins, D. R.; Curetty, L. L.; Levi, M. E.; Shen, Y.; Davis, L. S., and Norgard, M. V., 1995, Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic peptides activate monocytes/macrophages. J. Immunol. 154:2866–2877

    PubMed  CAS  Google Scholar 

  82. Rawadi, G., and Roman-Roman, S., 1996, Mycoplasma membrane lipoproteins induce proinflammatory cytokines by a mechanism distinct from that of lipopolysaccharide. Infect. Immun. 64:637–643

    PubMed Central  PubMed  CAS  Google Scholar 

  83. Rawadi, G.; Roman-Roman, S.; Castedo, M.; Dutilleul, V.; Susin, S.; Marchetti, P.; Geuskens, M., and Kroemer, G., 1996, Effects of Mycoplasma fermentons on the myelomonocytic lineage. J. Immunol. 156:670–678

    PubMed  CAS  Google Scholar 

  84. Rawadi, G.; Zugaza, J. L.; Lemercier, B.; Marvaud, J. C; Popoff, M.; Bertoglio, J., and Roman-Roman, S., 1999, Involvement of small GTPases in Mycoplasma fermentons membrane lipoproteins-mediated activation of macrophages. J. Biol. Chem. 274:30794–30798

    PubMed  CAS  Google Scholar 

  85. Razin, S.; Yogev, D., and Naot, Y., 1998, Molecular biology and pathogenicity of mycoplasmas. Microbiol. Mol. Biol. Rev. 62:1094–1156

    PubMed Central  PubMed  CAS  Google Scholar 

  86. Richards, A. L., 1997, Tumour necrosis factor and associated cytokines in the host’s response to malaria. Int. J. Parasitol. 27:1251–1263

    PubMed  CAS  Google Scholar 

  87. Rollins, S.; Colby, T., and Clayton, F., 1986, Open lung biopsy in Mycoplasma pneumoniae pneumonia. Arch. Pathol. Lab. Med. 110:34–41

    PubMed  CAS  Google Scholar 

  88. Rottem, S., and Markowitz, O., 1979, Unusual positional distribution of fatty acids in phosphatidylglycerol of sterol-requiring mycoplasmas. FEBS Letters 107:379–382

    PubMed  CAS  Google Scholar 

  89. Rowe, J. A.; Scragg, I. G.; Kwiatkowski, D.; Ferguson, D. J.; Carucci, D. J., and Newbold, C. I., 1998, Implication of mycoplasma contamination in Plasmodium falciparum cultures and methods of its detection and eradication. Mol. Biochem. Parasitol. 92:177–180

    PubMed  CAS  Google Scholar 

  90. Ruschmeyer, D.; Thude, H. J., and Mühlradt, P. F., 1993, MDHM, a macrophage-activating product from Mycoplasma fermentons, stimulates murine macrophages to synthesize nitric oxide and become tumoricidal. FEMS Immunol. Medical Microbiol. 7:223–230

    CAS  Google Scholar 

  91. Ruuth, E., and Lundgren, E., 1986, Enhancement of immunoglobulin secretion by the lymphokine-like activity of a Mycoplasma arginini strain. Scand. J. Immunol. 23:575–580

    PubMed  CAS  Google Scholar 

  92. Ruuth, E., and Praz, F., 1989, Interactions between mycoplasmas and the immune system. Immunol. Rev. 112:133–160

    PubMed  CAS  Google Scholar 

  93. Ruuth, E.; Ranby, M.; Friedrich, B.; Persson, H.; Goustin, A.; Leanderson, T.; Coutinho, A., and Lundgren, E., 1985, Mycoplasma mimicry of lymphokine activity in T-cell lines. Scand. J. Immunol. 21:593–600

    PubMed  CAS  Google Scholar 

  94. Sacht, G.; Märten, A.; Deiters, U.; Sübmuth, R.; Jung, G.; Wingender, E., and Mühlradt, P. F., 1998, Activation of nuclear factor-kappaB in macrophages by mycoplasmal lipopeptides. Eur. J. Immunol. 28:4207–4212

    PubMed  CAS  Google Scholar 

  95. Sankaran, K., and Wu, H. C., 1994, Lipid modification of bacterial prolipoprotein. J. Biol.Chem. 269:19701–19706

    PubMed  CAS  Google Scholar 

  96. Schaeverbeke, T.; Gilroy, C. B.; Bébéar, C; Dehais, J., and Taylor-Robinson, D., 1996, Mycoplasma fermentans in joints of patients with rheumatic arthritis and other joint disorders. Lancet 347:1418

    Google Scholar 

  97. Schaeverbeke, T.; Renaudin, H.; Clerc, M.; Lequen, L.; Vernhes, J. P.; De Barbeyrac, B.; Bannwarth, B.; Bébéar, C., and Dehais, J., 1997, Systematic detection of mycoplasmas by culture and polymerase chain reaction (PCR) procedures in 209 synovial fluid samples. Br. J. Rheumatol. 36:310–314

    PubMed  CAS  Google Scholar 

  98. Schimmelpfeng, L.; Langenberg, U., and Peters, J. H., 1980, Macrophages overcome mycoplasma infections of cells in-vitro. Nature 285:661–662

    PubMed  CAS  Google Scholar 

  99. Sher, T.; Yamin, A.; Rottem, S., and Gallily, R., 1990, In vitro induction of tumor necrosis factor a, tumor cytolysis and blast transformation by Spiroplasma membranes . J. Natl. Cancer Inst 82:1142–1145

    PubMed  CAS  Google Scholar 

  100. Siebenlist, U.; Franzoso, G., and Brown, K., 1994, Structure, regulation and function of NF-kB. Annu. Rev. Cell Biol. 10:405–455

    PubMed  CAS  Google Scholar 

  101. Sitia, R.; Rubartelli, A.; Deambrosis, S.; Pozzi, D., and Hämmerling, U., 1985, Differentiation of the murine B cell lymphoma 1.29: inductive capacities of lipopolysaccharide and Mycoplasma fermentans products. Eur. J. Immunol. 15:570

    PubMed  CAS  Google Scholar 

  102. Stuart, P. M., 1993, Mycoplasmal induction of cytokine production and major histocompatibility complex expression. Clinical Infectious Dis. 17(Suppl 1):S187-S191

    Google Scholar 

  103. Stuart, P. M.; Cassell, G. H., and Woodward, J. G., 1989, Induction of Class II MHC Antigen expression in macrophages by Mycoplasma species. J. Immunol. 142:3392–3399

    PubMed  CAS  Google Scholar 

  104. Stuart, P. M.; Cassell, G. H., and Woodward, J. G., 1990, Differential induction of bone marrow macrophage proliferation by mycoplasmas involves granulocyte-macrophage colony-stimulating factor. Infect. Immun. 58:3558–3563

    PubMed Central  PubMed  CAS  Google Scholar 

  105. Stuart, P. M.; Egan, R. M., and Woodward, J. G., 1993, Characterization of MHC induction by Mycoplasma fermentans (incognitus strain). Cell. Immunol. 152:261–270

    PubMed  CAS  Google Scholar 

  106. Stuehr, D. J.; Gross, S. S.; Sakuma, I.; Levi, R., and Nathan, C. F., 1989, Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J. Exp. Med. 169:1011–1020

    PubMed  CAS  Google Scholar 

  107. Sugama, K.; Kuwano, K.; Furukawa, M.; Himeno, Y.; Satoh, T., and Aral, S., 1990, Mycoplasma induce transcription and production of tumor necrosis factor in a monocytic cell line, THP1, by a protein kinase C-independent pathway. Infect. Immun. 58:3564–3567

    PubMed Central  PubMed  CAS  Google Scholar 

  108. Sultzer, B. M., 1968, Genetic control of leucocyte responses to Endotoxin. Nature (London) 219:1253–1254

    CAS  Google Scholar 

  109. Takema, M.; Oka, S.; Uno, K.; Nakamura, S.; Arita, H.; Tawara, K.; Inaba, K., and Muramatsu, S., 1991, Macrophage-activating factor extracted from mycoplasmas. Cancer Immunol Immunother. 33:39–44

    PubMed  CAS  Google Scholar 

  110. Takeuchi, O.; Takeda, K.; Hoshino, K.; Adachi, O.; Ogawa, T., and Akira, S., 2000, Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol. 12:113–117

    PubMed  CAS  Google Scholar 

  111. Takeuchi, O.; Kaufmann, A.; Grote, K.; Kawai, T.; Hoshino, K.; Morr, M.; Mühlradt, P. F., and Akira, S., 2000, Preferentially the R-stereoisomer of the mycoplasmal lipopeptide MALP-2 activates immune cells through a TLR2- and MyD88-dependent signaling pathway. J. Immunol. 164:558–561

    Google Scholar 

  112. Takeuchi, O.; Kawai, T.; Mühlradt, P. F.; Morr, M.; Radolf, J. D.,. Z. A.; Takeda, Y., and Akira, S., 2001, Discrimination of microbial lipoproteins by Tolllike receptor (TLR) 6. Int. Immunol. 13:933–940

    PubMed  CAS  Google Scholar 

  113. Tarshis, M.; Saltman, M., and Rottem, S., 1991, Fusion of Mycoplasmas: the formation of cell hybrids. FEMS Microbiol. Letters 82:67–72

    Google Scholar 

  114. Taylor, G., and Howard, C. J., 1980, Interaction of Mycoplasma pulmonis with mouse peritoneal macrophages and polymorphonuclear leucocytes. J. Med. Microbiol. 13:19–30

    PubMed  CAS  Google Scholar 

  115. Teh, H. S.; Ho, M., and Williams, L. D., 1988, Suppression of cytotoxic responses by a supernatant factor derived from Mycoplasma hyorhinis-infected mammalian cell lines. Infect. Immun. 56:197–203

    PubMed Central  PubMed  CAS  Google Scholar 

  116. Tracey, K. J., and Cerami, A., 1994, Tumor necrosis factor a pleiotropic cytokine and therapeutic agent. Annu. Rev. Med. 45:491–503

    PubMed  CAS  Google Scholar 

  117. Tuffrey, M. A.; Furr, P. M.; Falder, P., and Taylor-Robinson, D., 1984, The anti-Chlamydial effect of experimental Mycoplasma pulmonis infection in the murine genital tract. J. Med. Microbiol. 17:357–362

    PubMed  CAS  Google Scholar 

  118. Uno, K.; Takema, M.; Hidaka, S.; Tanaka, R.; Konishi, T.; Kato, T.; Nakamura, S., and Muramatsu, S., 1990, Induction of antitumor activity in macrophages by mycoplasmas in concert with interferon. Cancer Immunol. Immunother. 32:22–28

    PubMed  CAS  Google Scholar 

  119. Webster AD; Furr PM; Hughes-Jones NC; Gorick BD, and Taylor-Robinson D, 1988, Critical dependence on antibody for defence against mycoplasmas. Clin-Exp-Immunol. 71:383–387

    PubMed Central  PubMed  CAS  Google Scholar 

  120. Weinberg, J. B.; Smith, P. F., and Kahane, I., 1980, Bacterial lipopolysaccharides and mycoplasmal lipoglycans: a comparison between their abilities to induce macrophage-mediated tumor cell killing and limulus amebocyte lysate clotting. Biochem. Biophys. Res. Com. 97:493–499

    PubMed  CAS  Google Scholar 

  121. Weyer, K. A.; Schäfer, W.; Lottspeich, F., and Michel, H., 1987, The cytochrome subunit of the photosynthetic reaction center from Rhodopseudomonas viridis is a lipoprotein. Biochemistry 26:2909–2914

    CAS  Google Scholar 

  122. Wise, K. S.; Kim, M. F.; Theiss, P. M., and Lo, S.-C., 1993, A family of strain-variant surface lipoproteins of Mycoplasma fermentans. Infect. Immun. 61:3327–3333

    CAS  Google Scholar 

  123. Yang, G.; Coffman, F. D., and Wheelock, E. F., 1994, Characterization and purification of a macrophage-triggering factor produced in Mycoplasma arginini-infected L5178Y cell cultures. J. Immunol. 153:2579–2591

    PubMed  CAS  Google Scholar 

  124. Ziegler-Heitbrock, H. W., and Burger, R., 1987, Rapid removal of mycoplasma from cell lines mediated by a direct effect of complement. Exp. Cell. Res. 173:388–394

    PubMed  CAS  Google Scholar 

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  1. Immunobiology Research Group, Gesellschaft für Biotechnologische Forschung mbH, Mascheroderweg 1, D-38124, Braunschweig, Germany

    Peter F. Mühlradt

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  1. Peter F. Mühlradt
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  1. The Hebrew University-Hadassah Medical School, Jerusalem, Israel

    Shmuel Razin

  2. University of Heidelberg, Heidelberg, Germany

    Richard Herrmann

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Mühlradt, P.F. (2002). Immunomodulation by Mycoplasmas: Artifacts, Facts and Active Molecules. In: Razin, S., Herrmann, R. (eds) Molecular Biology and Pathogenicity of Mycoplasmas. Springer, Boston, MA. https://doi.org/10.1007/0-306-47606-1_20

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  • DOI: https://doi.org/10.1007/0-306-47606-1_20

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