Abstract
NK cells play an important regulatory role in sepsis by induction and augmentation of proinflammatory reactions in early stages of the septic process and by suppression of immune response in later stages of inflammation. The present work was aimed at the effect of bacterial lipopolysaccharide (LPS), the main pathogenic factor of sepsis development, on human NK cells ex vivo. We show that LPS activates immature CD57-negative NK cells, which typically constitute less than half of the normal NK cell population in human peripheral blood. Under conditions of NK cell stimulation with IL-2, addition of LPS provokes an increase in IFN-γ production. However, LPS both increased and inhibited NK cell cytotoxic activity. It is important to note that the activation of NK cells on LPS addition was observed in the absence of TLR4 on the NK cell surface. These results confirm our previous data arguing for a direct interaction of LPS with NK cells and evidence an atypical mechanism of LPS-induced NK cell activation without the involvement of surface TLR4.
Similar content being viewed by others
References
Yarilin, A. A. (2010) Immunology [in Russian], GEOTAR-Media, Moscow.
Thale, C., and Kiderlen, A. F. (2005) Sources of interferon-gamma (IFN-gamma) in early immune response to Listeria monocytogenes, Immunobiology, 210, 673–683.
Artavanis-Tsakonas, K., and Riley, E. M. (2002) Innate immune response to malaria: rapid induction of IFN-gamma from human NK cells by live Plasmodium falciparum-infected erythrocytes, J. Immunol., 169, 2956–2963.
Abakushina, E. V., Kuzmina, E. G., and Kovalenko, E. I. (2012) The main properties and functions of human NK cells, Immunologiya, 4, 220–225.
Chiche, L., Forel, J. M., Thomas, G., Farnarier, C., Vely, F., Blery, M., Papazian, L., and Vivier, E. (2011) The role of natural killer cells in sepsis, J. Biomed. Biotechnol., 2011, 986491.
Emoto, M., Miyamoto, M., Yoshizawa, I., Emoto, Y., Schaible, U. E., Kita, E., and Kaufmann, S. H. (2002) Critical role of NK cells rather than V alpha 14(+)NKT cells in lipopolysaccharide-induced lethal shock in mice, J. Immunol., 169, 1426–1432.
Cooper, M. A., Fehniger, T. A., Fuchs, A., Colonna, M., and Caligiuri, M. A. (2004) NK cell and DC interactions, Trends Immunol., 25, 47–52.
Gerosa, F., Baldani-Guerra, B., Nisii, C., Marchesini, V., Carra, G., and Trinchieri, G. (2002) Reciprocal activating interaction between natural killer cells and dendritic cells, J. Exp. Med., 195, 327–333.
Goodier, M. R., and Londei, M. (2000) Lipopolysaccharide stimulates the proliferation of human CD56+CD3-NK cells: a regulatory role of monocytes and IL-10, J. Immunol., 165, 139–147.
Godshall, C. J., Scott, M. J., Burch, P. T., Peyton, J. C., and Cheadle, W. G. (2003) Natural killer cells participate in bacterial clearance during septic peritonitis through interactions with macrophages, Shock, 19, 144–149.
Tu, Z., Bozorgzadeh, A., Pierce, R. H., Kurtis, J., Crispe, I. N., and Orloff, M. S. (2008) TLR-dependent cross talk between human Kupffer cells and NK cells, J. Exp. Med., 205, 233–244.
Chalifour, A., Jeannin, P., Gauchat, J. F., Blaecke, A., Malissard, M., N’Guyen, T., Thieblemont, N., and Delneste, Y. (2004) Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers α-defensin production, Blood, 104, 1778–1783.
Lauzon, N. M., Mian, F., MacKenzie, R., and Ashkar, A. A. (2006) The direct effects of Toll-like receptor ligands on human NK cell cytokine production and cytotoxicity, Cell Immunol., 241, 102–112.
Saikh, K. U., Lee, J. S., Kissner, T. L., Dyas, B., and Ulrich, R. G. (2003) Toll-like receptor and cytokine expression patterns of CD56+ T cells are similar to natural killer cells in response to infection with Venezuelan equine encephalitis virus replicons, J. Infect. Dis., 188, 1562–1570.
Mian, M. F., Lauzon, N. M., Andrews, D. W., Lichty, B. D., and Ashkar, A. A. (2010) FimH can directly activate human and murine natural killer cells via TLR4, Mol. Ther., 18, 1379–1388.
O’Connor, G. M., Hart, O. M., and Gardiner, C. M. (2005) Putting the natural killer cells in its place, Immunology, 117, 1–10.
Souza-Fonseca-Guimaraes, F., Parlato, M., Philippart, F., Misset, B., Cavaillon, J. M., and Adib-Conquy, M. (2012) Toll-like receptors expression and interferon-γ production by NK cells in human sepsis, Crit. Care, 16, R206.
Tadema, H., Abdulahad, W. H., Stegeman, C. A., Kallenberg, C. G., and Heeringa, P. (2011) Increased expression of Toll-like receptors by monocytes and natural killer cells in ANCA-associated vasculitis, PLoS One, 6, e24315.
Kanevskiy, L. M., Telford, W. G., Sapozhnikov, A. M., and Kovalenko, E. I. (2013) Lipopolysaccharide induces IFN-γ production in human NK cells, Front. Immunol., 4, 11.
Shibata, T., Motoi, Y., Tanimura, N., Yamakawa, N., Akashi-Takamura, S., and Miyake, K. (2011) Intracellular TLR4/MD-2 in macrophages senses Gram-negative bacteria and induces a unique set of LPS-dependent genes, Int. Immunol., 23, 503–510.
Hornef, M. W., Normark, B. H., Vandewalle, A., and Normark, S. (2003) Intracellular recognition of lipopolysaccharide by Toll-like receptor 4 in intestinal epithelial cells, J. Exp. Med., 198, 1225–1235.
Abo, T., and Balch, C. M. (1981) A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1), J. Immunol., 127, 1024–1029.
Luetke-Eversloh, M., Killig, M., and Romagnani, C. (2013) Signatures of human NK cell development and terminal differentiation, Front. Immunol., 4, 499.
Cavaillon, J. M., and Adib-Conquy, M. (2006) Bench-to-bedside review: endotoxin tolerance as a model of leukocyte reprogramming in sepsis, Crit. Care, 10, 233.
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.
Voshol, H., van Zuylen, C. W., Orberger, G., Vliegenthart, J. F., and Schachner, M. (1996) Structure of the HNK-1 carbohydrate epitope on bovine peripheral myelin glycoprotein P0, J. Biol. Chem., 271, 22957–22960.
Nielsen, C. M., White, M. J., Goodier, M. R., and Riley, E. M. (2013) Functional significance of CD57 expression on human NK cells and relevance to disease, Front. Immunol., 4, 422.
Lopez-Verges, S., Milush, J. M., Pandey, S., York, V. A., Arakawa-Hoyt, J., Pircher, H., Norris, P. J., Nixon, D. F., and Lanier, L. L. (2010) CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK cell subset, Blood, 116, 3865–3874.
Gayoso, I., Sanchez-Correa, B., Campos, C., Alonso, C., Pera, A., Casado, J. G., Morgado, S., Tarazona, R., and Solana, R. (2011) Immunosenescence of human natural killer cells, J. Innate Immun., 3, 337–343.
Kovalenko, E. I., Abakushina, E. V., Telford, W., Kapoor, V., Korchagina, E. Yu., Khaidukov, S. V., Molotkovskaya, I. M., Sapozhnikov, A. M., Vlaskin, P. A., and Bovin, N. V. (2007) Clustered carbohydrates as a target for natural killer cells: a model system, Histochem. Cell. Biol., 127, 313–326.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published in Russian in Biokhimiya, 2014, Vol. 79, No. 12, pp. 1636–1647.
Rights and permissions
About this article
Cite this article
Kanevskiy, L.M., Erokhina, S.A., Streltsova, M.A. et al. Bacterial lipopolysaccharide activates CD57-negative human NK cells. Biochemistry Moscow 79, 1339–1348 (2014). https://doi.org/10.1134/S0006297914120074
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0006297914120074