Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-30T15:42:38.789Z Has data issue: false hasContentIssue false
  • English
  • Français

The interplay between Leishmania promastigotes and human Natural Killer cells in vitro leads to direct lysis of Leishmania by NK cells and modulation of NK cell activity by Leishmania promastigotes

Published online by Cambridge University Press:  09 September 2011

THORSTEN LIEKE ,
SUSANNE NYLÉN ,
LIV EIDSMO ,
CHRISTEL SCHMETZ ,
LOUISE BERG  and
HANNAH AKUFFO
THORSTEN LIEKE*
Affiliation:
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden Transplant Laboratory, Department of General-, Visceral- and Transplantation Surgery, Medizinische Hochschule Hannover, D-30625 Hannover, Germany
SUSANNE NYLÉN
Affiliation:
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden
LIV EIDSMO
Affiliation:
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden
CHRISTEL SCHMETZ
Affiliation:
Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, Bernhard Nocht Strasse 74, 20359 Hamburg, Germany
LOUISE BERG
Affiliation:
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden Strategic Research Center, IRIS, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden
HANNAH AKUFFO
Affiliation:
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden
*
*Corresponding author: Transplantationlabor, Medical University of Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Tel: +49 511 5326317. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

NK cells represent one of the first lines of defence in the immune reaction after invasion of Leishmania parasites. Depletion of mouse natural killer (NK) cells dramatically enhances susceptibility of normally resistant mice. In this study we evaluated the fate of NK cells and parasites after contact formation. The hydrophilic fluorescent dye CMFDA (chloro-methylfluorescin diacetate) that allows analysis of cytotoxicity in flow cytometry and microscopy was used. Furthermore, these findings were confirmed with scanning and transmission electron microscopy. Direct contact points were found between Leishmania promastigotes and naïve human NK cells. These contacts were associated with transfer of cytosol by membrane bridges and cytotoxicity of NK cells against Leishmania. However, in contrast to other target cells which allow repeated exocytosis of lytic granules, contact with Leishmania causes immediate destruction of NK cells in a non-apoptotic way. Our results give a reasonable explanation for ex vivo observations of reduced NK cell numbers and impaired NK response in patients with acute cutaneous leishmaniasis. Animal models have clearly shown that NK cells play a key role in the induction and direction of the immune response. Thus inhibition of NK cells at the onset of infection would be advantageous for the survival of the parasite.

Keywords

cutaneous leishmaniasishuman NK cellsdirect recognitionlysis
Type
Research Article
Information
Parasitology , Volume 138 , Issue 14 , December 2011 , pp. 1898 - 1909
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Akuffo, H., Maasho, K., Blostedt, M., Hojeberg, B., Britton, S. and Bakhiet, M. (1997). Leishmania aethiopica derived from diffuse leishmaniasis patients preferentially induce mRNA for interleukin-10 while those from localized leishmaniasis patients induce interferon-gamma. Journal of Infectious Diseases 175, 737–741.CrossRefGoogle ScholarPubMed
Akuffo, H. O., Walford, C. and Nilsen, R. (1990). The pathogenesis of Leishmania aethiopica infection in BALB/c mice. Scandinavian Journal of Immunology 32, 103–110.CrossRefGoogle ScholarPubMed
Artavanis-Tsakonas, K., Eleme, K., McQueen, K. L., Cheng, N. W., Parham, P., Davis, D. M. and Riley, E. M. (2003). Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes. Journal of Immunology 171, 5396–5405.CrossRefGoogle ScholarPubMed
Becker, I., Salaiza, N., Aguirre, M., Delgado, J., Carrillo-Carrasco, N., Kobeh, L. G., Ruiz, A., Cervantes, R., Torres, A. P., Cabrera, N., Gonzalez, A., Maldonado, C. and Isibasi, A. (2003). Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2. Molecular and Biochemical Parasitology 130, 65–74.CrossRefGoogle ScholarPubMed
Belosevic, M., Finbloom, D. S., Van Der Meide, P. H., Slayter, M. V. and Nacy, C. A. (1989). Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. Journal of Immunology 143, 266–274.CrossRefGoogle ScholarPubMed
Bopp, T., Becker, C., Klein, M., Klein-Hessling, S., Palmetshofer, A., Serfling, E., Heib, V., Becker, M., Kubach, J., Schmitt, S., Stoll, S., Schild, H., Staege, M. S., Stassen, M., Jonuleit, H. and Schmitt, E. (2007). Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. Journal of Experimental Medicine 204, 1303–1310.CrossRefGoogle ScholarPubMed
Boyum, A. (1968). Separation of leukocytes from blood and bone marrow. Introduction. Scandinavian Journal of Clinical and Laboratory Investigation Supplement 97, 7–106.Google ScholarPubMed
Brittingham, A., Morrison, C. J., McMaster, W. R., McGwire, B. S., Chang, K. P. and Mosser, D. M. (1995). Role of the Leishmania surface protease gp63 in complement fixation, cell adhesion, and resistance to complement-mediated lysis. Journal of Immunology 155, 3102–3111.CrossRefGoogle ScholarPubMed
Bryceson, A. D. (1969). Diffuse cutaneous leishmaniasis in Ethiopia. I. The clinical and histological features of the disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 63, 708–737.CrossRefGoogle ScholarPubMed
Carrera, L., Gazzinelli, R. T., Badolato, R., Hieny, S., Muller, W., Kuhn, R. and Sacks, D. L. (1996). Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice. Journal of Experimental Medicine 183, 515–526.CrossRefGoogle ScholarPubMed
Cerwenka, A. and Lanier, L. L. (2001). Ligands for natural killer cell receptors: redundancy or specificity. Immunological Reviews 181, 158–169.CrossRefGoogle ScholarPubMed
Convit, J. and Kerdel-Vegas, F. (1965). Disseminated cutaneous leishmaniasis; innoculation to laboratory animals, electron microscopy and fluorescent antibodies studies. Archives of Dermatology 91, 439–447.CrossRefGoogle ScholarPubMed
Cooper, M. A., Fehniger, T. A., Turner, S. C., Chen, K. S., Ghaheri, B. A., Ghayur, T., Carson, W. E. and Caligiuri, M. A. (2001). Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood 97, 3146–3151.CrossRefGoogle ScholarPubMed
Descoteaux, A. and Turco, S. J. (2002). Functional aspects of the Leishmania donovani lipophosphoglycan during macrophage infection. Microbes and Infection 4, 975–981.CrossRefGoogle ScholarPubMed
Habibi, G. R., Khamesipour, A., McMaster, W. R. and Mahboudi, F. (2001). Cytokine gene expression in healing and non-healing cases of cutaneous leishmaniasis in response to in vitro stimulation with recombinant gp63 using semi-quantitative RT-PCR. Scandinavian Journal of Immunology 54, 414–420.CrossRefGoogle ScholarPubMed
Hatcher, F. M. and Kuhn, R. E. (1982). Destruction of Trypanosoma cruzi by natural killer cells. Science 218, 295–296.CrossRefGoogle ScholarPubMed
Ilgoutz, S. C. and McConville, M. J. (2001). Function and assembly of the Leishmania surface coat. International Journal for Parasitology 31, 899–908.CrossRefGoogle ScholarPubMed
Karre, K. (2002). NK cells, MHC class I molecules and the missing self. Scandinavian Journal of Immunology 55, 221–228.CrossRefGoogle ScholarPubMed
Korbel, D. S., Finney, O. C. and Riley, E. M. (2004). Natural killer cells and innate immunity to protozoan pathogens. International Journal for Parasitology 34, 1517–1528.CrossRefGoogle ScholarPubMed
Laskay, T., Diefenbach, A., Rollinghoff, M. and Solbach, W. (1995). Early parasite containment is decisive for resistance to Leishmania major infection. European Journal of Immunology 25, 2220–2227.CrossRefGoogle ScholarPubMed
Lieke, T., Graefe, S. E., Klauenberg, U., Fleischer, B. and Jacobs, T. (2004). NK cells contribute to the control of Trypanosoma cruzi infection by killing free parasites by perforin-independent mechanisms. Infection and Immunity 72, 6817–6825.CrossRefGoogle Scholar
Lieke, T., Nylen, S., Eidsmo, L., McMaster, W. R., Mohammadi, A. M., Khamesipour, A., Berg, L. and Akuffo, H. (2008). Leishmania surface protein gp63 binds directly to human natural killer cells and inhibits proliferation. Clinical and Experimental Immunology 153, 221–230.CrossRefGoogle ScholarPubMed
Maasho, K. and Akuffo, H. O. (1992). Cells from healthy non-exposed individuals produce cytokines to selected fractions of Leishmania promastigotes. Scandinavian Journal of Immunology Supplement 11, 179–184.CrossRefGoogle ScholarPubMed
Maasho, K., Sanchez, F., Schurr, E., Hailu, A. and Akuffo, H. (1998). Indications of the protective role of natural killer cells in human cutaneous leishmaniasis in an area of endemicity. Infection and Immunity 66, 2698–2704.CrossRefGoogle Scholar
Newman, K. C. and Riley, E. M. (2007). Whatever turns you on: accessory-cell-dependent activation of NK cells by pathogens. Nature Reviews Immunology 7, 279–291.CrossRefGoogle ScholarPubMed
Nylen, S., Maasho, K., Soderstrom, K., Ilg, T. and Akuffo, H. (2003). Live Leishmania promastigotes can directly activate primary human natural killer cells to produce interferon-gamma. Clinical and Experimental Immunology 131, 457–467.CrossRefGoogle ScholarPubMed
Nylen, S., Mortberg, U., Kovalenko, D., Satti, I., Engstrom, K., Bakhiet, M. and Akuffo, H. (2001). Differential induction of cellular responses by live and dead Leishmania promastigotes in healthy donors. Clinical and Experimental Immunology 124, 43–53.CrossRefGoogle ScholarPubMed
Russell, D. G. (1987). The macrophage-attachment glycoprotein gp63 is the predominant C3-acceptor site on Leishmania mexicana promastigotes. European Journal of Biochemistry 164, 213–221.CrossRefGoogle ScholarPubMed
Scharton, T. M. and Scott, P. (1993). Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. Journal of Experimental Medicine 178, 567–577.CrossRefGoogle ScholarPubMed
Schleicher, U., Liese, J., Knippertz, I., Kurzmann, C., Hesse, A., Heit, A., Fischer, J. A., Weiss, S., Kalinke, U., Kunz, S. and Bogdan, C. (2007). NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs. Journal of Experimental Medicine 204, 893–906.CrossRefGoogle ScholarPubMed
Stinchcombe, J. C., Bossi, G., Booth, S. and Griffiths, G. M. (2001). The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15, 751–761.CrossRefGoogle ScholarPubMed
Zambrano-Villa, S., Rosales-Borjas, D., Carrero, J. C. and Ortiz-Ortiz, L. (2002). How protozoan parasites evade the immune response. Trends in Parasitology 18, 272–278.CrossRefGoogle ScholarPubMed