Skip to main content

Ehrlichial Strategy for Survival and Proliferation in Leukocytes

  • Chapter
Bacterial Invasion into Eukaryotic Cells

Part of the book series: Subcellular Biochemistry ((SCBI,volume 33))

Abstract

Ehrlichial organisms classified in the family Rickettsiaceae, are uniquely adapted to survive and proliferate in primary host defensive cells such as monocytes and granulocytes. Recent success in culturing ehrlichial organisms in leukemia cell lines enabled us to apply molecular and cell biologic techniques for their characterization. Ehrlichial major outer membrane protein antigens are encoded by a large number of polymorphic multigenes conserved among related species. Both ligand and receptor for monocytic ehrlichial binding are proteins. For internalization and proliferation of ehrlichial organisms Ca2+-calmodulin and protein tyrosine phosphorylation are required. Monocytic and granulocytic ehrlichial organisms enter and maintain distinct cytoplasmic compartments which do not fuse with each other or lysosomes. Binding of monocytic ehrlichiae to macrophage surface induces rapid protein kinase A activation, leading to interference of signal transduction in the host cells such as Jak-Stat pathway or down regulation of class II antigen in response to interferon-γ. Altogether ehrlichial organisms upon contact with phagocytic leukocytes maim multiple innate microbicidal activity directed to them.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Barlough, J.E., Reubel, G.H., Madigan, J.E., Vredevoe, L.K., Miller, P.E., Miller, and Rikihisa, Y., 1998, Detection of Ehrlichia risticii, the agent of Potomac horse fever, in freshwater stream snails (Pleuroceridae: Juga spp.) of Northern California, J. Appl. Environ. Microbiol. 64: 2888–2893.

    CAS  Google Scholar 

  • Barnewall, R.E., and Rikihisa, Y., 1994, Abrogation of interferon-y induced inhibition of Ehrlichia chaffeensis infection in human monocytes with iron transferrin, Infect. Immun. 62: 4804–4810.

    CAS  PubMed  Google Scholar 

  • Barnewall, R.E., Rikihisa, Y., and Lee, E.H., 1997, Ehrlichia chaffeensis inclusions are early endosomes which selectively accumulate transferrin receptor. Infect. Immun. 65: 1455–1461.

    CAS  Google Scholar 

  • Barnewall, R.E., Ohashi, N., and Rikihisa, Y., 1999, Ehrlichia chaffeensis and E. sennetsu, but not the Human granulocyte ehrlichiosis agent colocalize with transferrin receptor and up-regulate transferrin receptor mRNA by activating iron-responsive protein 1. Infect Immun. 67: 2258–2265.

    CAS  Google Scholar 

  • Baynes, R., Bukofzer, G., Bothwell, T., Bezwoda, W., and Macfarlane, B., 1987, Transferrin receptors and transferrin iron uptake by cultured human blood monocytes, Eur. J. Cell. Biol. 43: 372–376.

    CAS  PubMed  Google Scholar 

  • Byrd, T.F, and Horowitz, M.A., 1989, Interferon gamma-activated human monocytes down regulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumonphila by limiting the availability of iron, J. Clin. Invest. 83: 1457–1465.

    Article  CAS  PubMed  Google Scholar 

  • Carlin, J.M., Borden, E.C., and Byrne, G.I., 1989, Interferon-induced indoleamine 2,3dioxygenase activity inhibits Chlamydia psittaci replication in human macrophages, J. Interferon Res. 9: 329–337.

    Article  CAS  PubMed  Google Scholar 

  • Chen, S-M., Popov, V.L,. Feng, H-M., and Walker, D.H., 1996, Antigenic diversity among strains of Ehrlichia chaffeensis, in: Proceedings of the 5th International Symposium on Rickettsiae and Rickettsial Diseases (Bratislava, Slovak Republic), Slovak Academy of Sciences, Bratislava, Slovak Republic, International Society of Rickettsiae and Rickettsial Diseases, pp. 329–334.

    Google Scholar 

  • Dumler, J.S., and Bakken, J.S. 1998, Human ehrlichiosis: Newly recognized infections transmitted by ticks, Annu. Rev. Med. 49: 201–213.

    Article  CAS  PubMed  Google Scholar 

  • French, D.M., McElwain, T.F., McGuire, T.C., and Palmer, G., 1998, Expression of Anaplasma marginale major surface protein 2 variants, during persistent cyclic rickettsemia, Infect. Immun. 66: 1200–1207.

    CAS  PubMed  Google Scholar 

  • Fukuda, T., Sasahara, T., and Kitao, T., 1973, Studies on the causative agent of Hyuganetsu disease, XI. Characteristics of rickettsia-like organism isolated from metacercaria of Stellantchasmus falcatus parasitic in grey mullet, J. Jap. Assoc. Infect. Dis., 47:474–482 (text in Japanese).

    Google Scholar 

  • Iyengar, R., Stuehr, D.J., and Marietta, M.A., 1987, Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: Precursors and role of the respiratory burst, Proc. Natl. Acad. Sci. USA 84: 6369–6373.

    Article  CAS  PubMed  Google Scholar 

  • Isberg; R.R., 1991, Discrimination between intracellular uptake and surface adhesion of bacterial pathogens, Science 252: 934–938.

    Article  PubMed  Google Scholar 

  • Kawahara, M., Suto, C., Shibata, S., Futohashi, M., and Rikihisa, Y., 1996, Impaired antigen specific responses and enhanced polyclonal stimulation in mice infected with Ehrlichia muris, Microbiol. Immunol. 40: 575–587.

    CAS  PubMed  Google Scholar 

  • Kihlstrom, E., and Soderlund, G., 1983, Trifluoperazine inhibits the infectivity of Chlamydia trachomatis for McCoy cells, FEMS Microbiology letters. 20: 119–123.

    Article  Google Scholar 

  • Lee, E., and Rikihisa, Y.,1996, Lack of TNF-a, IL-6, and GM-CSF but presence of IL-113, IL-8, and IL-10 expression in human monocytes exposed to viable or killed Ehrlichia chaffeensis, Infect. Immun. 64: 4211–4219.

    Google Scholar 

  • Lee, E., and Rikihisa, Y., 1997, Anti-Erhlichia chaffeensis antibody induces potent proinflammatory cytokine mRNA expression in human monocytes exposed to E. chaffeensis through sustained reduction of IkB-a and activation of NF-kB, Infect. Immun. 65: 2890–2897.

    CAS  Google Scholar 

  • Lee, E., and Rikihisa, Y., 1998, Protein kinase A-mediated inhibition of interferongamma-induced tyrosine phosphorylation of Janus kinases and latent cytoplasmic transcription factors in human monocytes by Ehrlichia chaffeensis, Infect. Immun. 66: 2514–2520.

    CAS  PubMed  Google Scholar 

  • Mengaud, J., Ohayon, H., Gounon, P., Mege, R-M., and Cossart, P., 1996, E-cadherin is the receptor for internalin, a surface protein required for entry of L.monocytogenes into epithelial cells, Cell 84: 923–932.

    Article  CAS  PubMed  Google Scholar 

  • Messick, J.B., and Rikihisa, Y., 1992, Suppression of I-A° on P388D, cells by Ehrlichia risticii infection in response to gamma interferon, Vet. Immunol. Immunopathol. 32: 225–241.

    Article  CAS  PubMed  Google Scholar 

  • Messick, J.B., and Rikihisa, Y., 1993, Characterization of Ehrlichia risticii binding, internalization, and growth in host cells by flow cytometry, Infect. Immun. 61: 3803–3810.

    CAS  PubMed  Google Scholar 

  • Messick, J.B., and Rikihisa, Y., 1994, Inhibition of binding, entry or survival of Ehrlichia risticii in P388DI cells by anti-E. risticii IgG and Fab fragments, Infect. Immun. 62: 3156–3161.

    CAS  PubMed  Google Scholar 

  • Misao, T., and Katsuta, K. 1956, Epidemiology of infectious mononucleosis, Jap. J. Clin. Exp. Med. 33: 73–82.

    Google Scholar 

  • Mott, J., Barnewall R., and Rikihisa, Y., 1999, Human granulocytic ehrlichiosis agent and Ehrlichia chaffeensis reside in different cytoplasmic compartments in HL-60 cells, Infect. Immun. 67: 1368–1378.

    CAS  PubMed  Google Scholar 

  • Mott, J., and Rikihisa, Y., 1999, Human granulocytic ehrlichiosis agent inhibition of superoxide anion generation in human neutrophils require contact of viable organisms with the host cell. American Society for Microbiology, Chicago, IL, June, 1999, Abstract in press.

    Google Scholar 

  • Moulder, J.W., 1985, Comparative biology of intracellular parasitism, Microbiol. Rev. 49: 298–337.

    CAS  PubMed  Google Scholar 

  • Nunez, M-T, Gaete, V., Watkins, J.A., and Glass, J., 1990, Mobilization of iron from endocytic vesicles, J. Biol. Chem. 265: 6688–6692.

    CAS  PubMed  Google Scholar 

  • Ohashi, N., Unver, A., and Rikihisa, Y., 1998a, Cloning and expression of immunodominant 30 kDa major outer membrane protein of Ehrlichia canis and application of the recombinant protein for serodiagnosis, J. Clin. Microbiol. 36: 2671–2680.

    CAS  PubMed  Google Scholar 

  • Ohashi, N., Zhi, N., Zhang, Y., and Rikihisa, Y., 1998b, Immunodominant major outer membrane proteins of Ehrlichia chaffeensis are encoded by a polymorphic multigene family, Infect. Immun. 66: 132–139.

    CAS  PubMed  Google Scholar 

  • Palmer, G.H., Aid, G., Barbet, A.F., McGuire, T.C., and McElwain, T.F., 1994, The immunoprotective Anaplasma marginale major surface protein 2 is encoded by a polymorphic multigene family, Infect. Immun. 62: 3808–3816.

    CAS  PubMed  Google Scholar 

  • Park, J., and Rikihisa, Y., 1991, Inhibition of Ehrlichia risticii growth in murine peritoneal macrophage by gamma interferon, calcium ionophore, and concanavalin A, Infect. Immun. 59: 3418–3423.

    CAS  PubMed  Google Scholar 

  • Park, J., and Rikihisa, Y., 1992, L-arginine-dependent killing of intracellular Ehrlichia risticii by macrophages treated with interferon-gamma, Infect. Immun. 60: 3504–3508.

    CAS  PubMed  Google Scholar 

  • Payne, N.R., and Horwitz, M.A., 1987, Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors, J. Exp. Med.166:1377–1389.

    Google Scholar 

  • Perez, M., Rikihisa,Y., and Wen, B., 1996, Antigenic and genetic characterization of anEhrlichia canis-like agent isolated from a human in Venezuela, J. Clin. Microbiol. 34: 2133–2139.

    CAS  Google Scholar 

  • Reddy, R.G., Sulsona, C.R., Harrison, R.H., Mahan, S.M., Burridge, M.J., and Barbet A.F., 1996, Sequence heterogeneity of the major antigenic protein 1 genes from Cowdria ruminantium isolates from different geographical areas, Clin. Diagn. Lab. Immunol. 3: 417–422.

    CAS  PubMed  Google Scholar 

  • Reubel, G.H., Barlough, J.E., and Madigan, J.E., 1998, Production and characterization of E. risticii, the agent of Potomac horse fever, from snails (Pleuroceridae: Alga spp.) in aquarium culture and genetic comparison to equine strains, J. Clin. Microbio!. 36: 1501–1511.

    CAS  Google Scholar 

  • Rikihisa, Y., 1990a, Ultrastructure of rickettsiae with special emphasis on ehrlichia, in: Ehrlichiosis: A Vector-Borne Disease of Animals and Humans, ( J.C. Williams and I. Kakoma eds.), Kluwer Academic Pubishers, Boston, Mass., p. 22–31

    Google Scholar 

  • Rikihisa, Y. 1990b,.Growth of Ehrlichia risticii in human colonic epithelial cells, in: Rickettsiology: Current issues and perspectives, 590, (K. Hechemy, ed.), New York Acad. Sci., NY., pp. 104–110.

    Google Scholar 

  • Rikihisa, Y., 1991, The tribe Ehrlichieae and ehrlichial diseases, Clin. Microbiol. Rev. 4:286–308. Rikihisa, Y., 1995, Ehrlichial Diseases, in: Zoonotic Diseases, Clin. Microbiol. 22, 413–419 (In Japanese).

    Google Scholar 

  • Rikihisa, Y., 1996, Ehrlichiae, in: Proceedings of the 5th International Symposium on Rickettsiae and Rickettsia! Diseases (Bratislava, Slovak Republic), Slovak Academy of Sciences, Bratislava, Slovak Republic, International Society of Rickettsiae and Rickettsial Diseases, pp. 272–286.

    Google Scholar 

  • Rikihisa, Y., 1997, Ehrlichiae, emerging human pathogens, in: Proceedings of the 2nd International Symposium on Lyme Disease, Shizuoka, Japan, pp. 332–345.

    Google Scholar 

  • Rikihisa, Y., 1999a, Ehrlichiae of veterinary importance, in: Proceedings of the 6`“ International Symposium on Rickettsiae and Rickettsial Diseases (Marseille, France), Elsevior, Paris, International Society of Rickettsiae and Rickettsial Diseases, In press.

    Google Scholar 

  • Rikihisa, Y., 1999b, Clinical and biological aspects of infections caused by Ehrlichia chaffeensis, Microb. Infect. 3: 1–10.

    Google Scholar 

  • Rikihisa, Y., Ewing, S.A., and Fox, J.C., 1994, Western immunoblot analysis of E. chaffeensis, E. canis or E. ewingii infection of dogs and humans, J. Clin. Microbiol. 32: 2107–2112.

    CAS  PubMed  Google Scholar 

  • Rikihisa, Y., Kawahara, M., Wen, B., Kociba, G., Fuerst, P., Kawamori, E, Suto, C., Shiba, S., and Futohashi, M., 1997, Western immunoblot analysis of Haemobartonella muris and comparison of 16S rDNA sequences of H. muris, H. fells, and Eperythrozoon suis, J. Clin. Microbiol. 35: 823–829.

    CAS  PubMed  Google Scholar 

  • Rikihisa, Y., Johnson, G.J, Wang, Y.-Z., Reed, S.M., Fertel, R., and Cooke, H.J., 1992, Loss of adsorptive capacity for sodium chloride as a cause of diarrhea in Potomac horse fever, Res. Vet. Sci. 52: 353–362.

    Article  CAS  PubMed  Google Scholar 

  • Rikihisa, Y., Pretzman, C.I., Johnson, G.C., Reed, S.M., Yamamoto, S., and Andrews, E. 1988, Clinical and immunological responses of ponies to Ehrlichia sennetsu and subsequent Ehrlichia risticii challenge, Infect. Immun. 56: 2960–2966.

    CAS  PubMed  Google Scholar 

  • Rikihisa, Y., Zhang, Y., and Park, J., 1994, Role of clathrin, microfilament, and microtubule on infection of mouse peritoneal macrophages with Ehrlichia risticii, Infect. Immun. 62: 5126–5132.

    CAS  PubMed  Google Scholar 

  • Rikihisa, Y., Zhang, Y., and Park, J., 1995, Role of Cat’ and calmodulin on ehrlichial survival in macrophages, Infect. Immun. 63: 2310–2316.

    CAS  PubMed  Google Scholar 

  • Rikihisa, Y., Zhi, N., Wormser, G. Wen, B., Horowitz, H.W., and Hechemy, K.E., 1997, Direct isolation and cultivation of human granulocytic ehrlichia from a human patien, J. Infect. Dis. 175: 210–213.

    CAS  Google Scholar 

  • Ristic, M., and Huxsoll, D., 1984, Tribe II, Ehrlichiae., in: Bergey’s Manual of Systematic Bacteriology, Vol. 1., ( N.R. Krieg and J.G. Holt, eds.), The Williams and Wilkins Co., Baltimore, MD., p. 704–711.

    Google Scholar 

  • Rydkina, E., Roux, V., Balayeva, N., and Raoult, D., 1996, Determination of the genome size of ehrlichiae by pulsed-field gel electrophoresis, in: Proceedings of the 5th International Symposium on Rickettsiae and Rickettsia! Diseases (Bratislava, Slovak Republic), Slovak Academy of Sciences, Bratislava, Slovak Republic, International Society of Rickettsiae and Rickettsial Diseases, pp. 318–323.

    Google Scholar 

  • Shainklin-Kestenbaum, R., Winikoff, Y., Kol, R., Chaimovitz, C., and Sayou, I., 1989, Inhibition of growth of Chlamydia trachomatis by the calcium antagonist verapamil, J. Gen. Microbiol. 135: 1619–1623.

    Google Scholar 

  • Snyder, S.H., and Bredt, D.S., 1992, Biological roles of nitric oxide, Sci. Am. 68–77.

    Google Scholar 

  • Solderland, G., and Kihlstrom, E., 1983, Effect of methylamine and monodansylcadaverine on the susceptibility of McCoy cells to Chlammydia trachomatis infection, Infect. Immun. 40: 531–541.

    Google Scholar 

  • Sumner, J.W., Nicholson, W.L., and Massung, R.E., 1997, PCR amplification and comparison of nucleotide sequences from the groESL heat shock operon of Ehrlichia spp., J. Clin. Microbiol. 35: 2087–2092.

    CAS  PubMed  Google Scholar 

  • Sumner, J.W., Sims, K.G., Jones, D.C., and Anderson, B.E., 1993, Ehrlichia chaffeensis expresses an immunoreactive protein homologous to the Escherichia coli GroEL protein, Infect. Immun. 61: 3536–3539.

    CAS  Google Scholar 

  • van Heeckeren, A., Rikihisa, Y., Park, J., and Fertel, R., 1993, TLmor necrosis factor-a, Interleukin-la, Interleukin-6 and prostaglandin E2 production in murine peritoneal macrophages infected with Ehrlichia ristici, Infect. Immun. 61: 4333–4337.

    PubMed  Google Scholar 

  • van Viet, A.M., Jongejan, F., von Kleef, M., and van der Zeijst, B.A.M., 1994, Molecular cloning, sequence analysis, and expression of the gene encoding the immunodominant 32kilodalton protein of Cowdria ruminantium, Infect. Immun. 62: 1451–1456.

    Google Scholar 

  • Walker, D.H., and Dumler, J.S., 1996, Emergence of ehrlichiosis as a human health problems, Emerging Infect. Dis. 2: 18–29.

    Article  CAS  PubMed  Google Scholar 

  • Weiss, E., Dasch, G.A., Kang, Y-H., and Westfall, H.N., 1988, Substrate utilization by Ehrlichia sennetsu and Ehrlichia risticii separated from host constituents by renografin gradient centrifugation, J. Bacteriol. 170: 5012–5017.

    CAS  PubMed  Google Scholar 

  • Weiss, E., Williams, J.C., Dasch, G.A., and Kang, Y H.,1989, Energy metabolism of monocytic Ehrlichia, Proc. Natl. Acad. Sci. USA 866: 1674–1678.

    Google Scholar 

  • Wells, M.Y., and Rikihisa, Y., 1988, Lack of lysosomal fusion with phagosomes containing Ehrlichia risticii in P388DI cells: Abrogation of inhibition with oxytetracycline, Infect. Immun. 56: 3209–3215.

    CAS  PubMed  Google Scholar 

  • Wen, B., Rikihisa, Y., Yamamoto, S., and Fuerst, P., 1996, Characterization of SF agent, an Ehrlichia sp. isolated from Stellantchasmus falcatus fluke, by 16S rRNA base sequence, serological, and morphological analysis, Int. J. Syst. Bacteriol. 46: 149–154.

    Article  CAS  PubMed  Google Scholar 

  • Yu, X-J., Crocquet-Valdes, P., and Walker, D.H., 1997, Cloning and sequencing of the gene for a 120 kDa immunodominant surface protein of Ehrlichia chaffeensis, Gene 184: 149–154.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Q-Y., Deryckere, D., Lauer, P., and Koomey, M., 1992, Gene conversion in Neisseria gonorrhoeae: evidence for its role in pilus antigenic variation, Proc. Nat. Acad. Sci. USA. 89: 5366–5370.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Y., Ohashi, N., Lee, E., and Rikhisa, Y., 1997, Ehrlichia sennetsu groE operon and antigenic properties of the GroEL homolog, FEMS Immun!. Med. Microbiol. 18 :39–46.

    Google Scholar 

  • Zhang, Y., and Rikihisa, Y., 1997, Tyrosine phosphorylation is required for ehrlichial internalization and replication in P388D, cells, Infect. Immun. 65: 2959–2964.

    CAS  PubMed  Google Scholar 

  • Zhang, Y., Ohashi, N., and Rikihisa, Y., 1998a, Cloning of the heat shock protein 70 (HSP70) of Ehrlichia sennetsu and differential expression of HSP70 and HSP60mRNA after temperature upshift, Infect. Immun. 66: 3106–3112.

    CAS  PubMed  Google Scholar 

  • Zhang, Y., Rikihisa, Y., Ohashi, N., and Zhi, N., 1998b, Binding of major outer membrane proteins of Ehrlichia chaffeensis to DH82 cell surface, submitted.

    Google Scholar 

  • Zhi, N., Rikihisa, Y H., Kim, Y., Wormser, G.P., and Horowitz, H.W., 1997, Comparison of major antigenic proteins of six strains of human granulocytic ehrlichiosis agents by Western immnoblot analysis, J. Clin. Microbiol. 35: 2606–2611.

    CAS  PubMed  Google Scholar 

  • Zhi, N., Ohashi, N., Rikihisa, Y., Horowitz, H.W., Womser, G.E. Hechemy, K., 1998, Cloning and expression of 44 kDa major outer membrane protein antigen gene of human granulocytic ehrlichiosis agent and application of the recombinant protein to serodiagnosis, J. Clin. Microbiol. 36: 1666–1673.

    CAS  Google Scholar 

  • Zhi, N.,Ohashi N., and Rikihisa, Y., 1999, Characterization of the expressed genes in p44 multi-gene family encoding major antigenic outer membrane proteins of the human granulocytic ehrlichiosis agent in HL-60 cells, American Society for Microbiology, Chicago, IL, June, 1999, Abstract in press.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Rikihisa, Y. (2000). Ehrlichial Strategy for Survival and Proliferation in Leukocytes. In: Oelschlaeger, T.A., Hacker, J. (eds) Bacterial Invasion into Eukaryotic Cells. Subcellular Biochemistry, vol 33. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4580-1_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-4580-1_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3330-0

  • Online ISBN: 978-1-4757-4580-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics