Abstract
Gram-negative bacteria have been shown to activate human natural killer (NK) cells. In this report, we show that the gram-positive bacterium Listeria monocytogenes can also activate human NK cells with regard to non-major histocompatibility complex (MHC)-restricted killing and the production of cytokines. Overnight incubation of peripheral blood mononuclear (PBM) cells or enriched NK cell populations with live or Formalin-fixed L. monocytogenes resulted in high levels of non-MHC-restricted cytotoxic activity. Listeria-stimulated non-MHC-restricted cytotoxic activity could be achieved with pathogenic as well as nonpathogenic Listeria strains. PBM cells also produced tumor necrosis factor alpha and different interferons (IFNs) after incubation with Listeria strains. Optimal cytokine production appeared to be dependent on nylon wool- and plastic-adherent cells. Different IFNs were produced by Listeria-stimulated PBM cells obtained from different donors. IFN-gamma was always produced but was sometimes associated with IFN-alpha and/or IFN-beta. Interleukin-2 (IL-2) activity was never detected in culture supernatants obtained from Listeria-stimulated PBM cell cultures. However, IL-2 appeared to be produced by Listeria-stimulated PBM cells, since antibody to IL-2 inhibited Listeria-stimulated NK cell cytotoxic activity. Listeria activation of NK cell cytotoxic activity was also dependent on tumor necrosis factor alpha production. Antibody to IFN-gamma, IFN-beta, or IFN-alpha had no effect on Listeria-stimulated NK cell cytotoxic activity. These results demonstrate that NK cells can be activated by Listeria strains and add further evidence that NK cells may play an important role in host defense against bacterial infections.
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Selected References
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- Bancroft G. J., Sheehan K. C., Schreiber R. D., Unanue E. R. Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice. J Immunol. 1989 Jul 1;143(1):127–130. [PubMed] [Google Scholar]
- Bankhurst A. D., Imir T. The mechanisms involved in the activation of human natural killer cells by staphylococcal enterotoxin B. Cell Immunol. 1989 Aug;122(1):108–121. doi: 10.1016/0008-8749(89)90152-4. [DOI] [PubMed] [Google Scholar]
- Buchmeier N. A., Schreiber R. D. Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7404–7408. doi: 10.1073/pnas.82.21.7404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleveland M. G., Ramirez R. B., Klimpel G. R. IFN-beta production by macrophages obtained from mice undergoing graft vs host disease. J Immunol. 1988 Dec 1;141(11):3823–3827. [PubMed] [Google Scholar]
- Cluff C. W., Garcia M., Ziegler H. K. Intracellular hemolysin-producing Listeria monocytogenes strains inhibit macrophage-mediated antigen processing. Infect Immun. 1990 Nov;58(11):3601–3612. doi: 10.1128/iai.58.11.3601-3612.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dempsey R. A., Dinarello C. A., Mier J. W., Rosenwasser L. J., Allegretta M., Brown T. E., Parkinson D. R. The differential effects of human leukocyte pyrogen/lymphocyte-activating factor, T cell growth factor, and interferon on human natural killer activity. J Immunol. 1982 Dec;129(6):2504–2510. [PubMed] [Google Scholar]
- Fleischmann W. R., Jr, Georgiades J. A., Osborne L. C., Johnson H. M. Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon. Infect Immun. 1979 Oct;26(1):248–253. doi: 10.1128/iai.26.1.248-253.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gaillard J. L., Berche P., Sansonetti P. Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect Immun. 1986 Apr;52(1):50–55. doi: 10.1128/iai.52.1.50-55.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garcia-Peñarrubia P., Koster F. T., Kelley R. O., McDowell T. D., Bankhurst A. D. Antibacterial activity of human natural killer cells. J Exp Med. 1989 Jan 1;169(1):99–113. doi: 10.1084/jem.169.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Havell E. A., Sehgal P. B. Tumor necrosis factor-independent IL-6 production during murine listeriosis. J Immunol. 1991 Jan 15;146(2):756–761. [PubMed] [Google Scholar]
- Holmberg L. A., Ault K. A. Characterization of natural killer cells induced in the peritoneal exudates of mice infected with Listeria monocytogenes: a study of their tumor target specificity and their expression of murine differentiation antigens and human NK-associated antigens. Cell Immunol. 1984 Nov;89(1):151–168. doi: 10.1016/0008-8749(84)90206-5. [DOI] [PubMed] [Google Scholar]
- Klimpel G. R., Infante A. J., Patterson J., Hess C. B., Asuncion M. Virus-induced interferon alpha/beta (IFN-alpha/beta) production by T cells and by Th1 and Th2 helper T cell clones: a study of the immunoregulatory actions of IFN-gamma versus IFN-alpha/beta on functions of different T cell populations. Cell Immunol. 1990 Jul;128(2):603–618. doi: 10.1016/0008-8749(90)90052-s. [DOI] [PubMed] [Google Scholar]
- Klimpel G. R., Niesel D. W., Asuncion M., Klimpel K. D. Natural killer cell activation and interferon production by peripheral blood lymphocytes after exposure to bacteria. Infect Immun. 1988 Jun;56(6):1436–1441. doi: 10.1128/iai.56.6.1436-1441.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klimpel G. R., Niesel D. W., Klimpel K. D. Natural cytotoxic effector cell activity against Shigella flexneri-infected HeLa cells. J Immunol. 1986 Feb 1;136(3):1081–1086. [PubMed] [Google Scholar]
- Klimpel G. R., Shaban R., Niesel D. W. Bacteria-infected fibroblasts have enhanced susceptibility to the cytotoxic action of tumor necrosis factor. J Immunol. 1990 Jul 15;145(2):711–717. [PubMed] [Google Scholar]
- Lindemann R. A. Bacterial activation of human natural killer cells: role of cell surface lipopolysaccharide. Infect Immun. 1988 May;56(5):1301–1308. doi: 10.1128/iai.56.5.1301-1308.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindemann R. A. Roles of interferon and cellular adhesion molecules in bacterial activation of human natural killer cells. Infect Immun. 1989 Jun;57(6):1702–1706. doi: 10.1128/iai.57.6.1702-1706.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakane A., Minagawa T. Alternative induction of IFN-alpha and IFN-gamma by Listeria monocytogenes in human peripheral blood mononuclear leukocyte cultures. J Immunol. 1981 Jun;126(6):2139–2142. [PubMed] [Google Scholar]
- Nakane A., Minagawa T., Kato K. Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection. Infect Immun. 1988 Oct;56(10):2563–2569. doi: 10.1128/iai.56.10.2563-2569.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakane A., Minagawa T., Kohanawa M., Chen Y., Sato H., Moriyama M., Tsuruoka N. Interactions between endogenous gamma interferon and tumor necrosis factor in host resistance against primary and secondary Listeria monocytogenes infections. Infect Immun. 1989 Nov;57(11):3331–3337. doi: 10.1128/iai.57.11.3331-3337.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakane A., Numata A., Asano M., Kohanawa M., Chen Y., Minagawa T. Evidence that endogenous gamma interferon is produced early in Listeria monocytogenes infection. Infect Immun. 1990 Jul;58(7):2386–2388. doi: 10.1128/iai.58.7.2386-2388.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pine L., Weaver R. E., Carlone G. M., Pienta P. A., Rocourt J., Goebel W., Kathariou S., Bibb W. F., Malcolm G. B. Listeria monocytogenes ATCC 35152 and NCTC 7973 contain a nonhemolytic, nonvirulent variant. J Clin Microbiol. 1987 Nov;25(11):2247–2251. doi: 10.1128/jcm.25.11.2247-2251.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rönnblom L., Forsgren A., Alm G. V. Characterization of interferons induced by bacteria and interferon-producing leukocytes in human peripheral blood. Infect Immun. 1983 Apr;40(1):126–132. doi: 10.1128/iai.40.1.126-132.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Safley S. A., Cluff C. W., Marshall N. E., Ziegler H. K. Role of listeriolysin-O (LLO) in the T lymphocyte response to infection with Listeria monocytogenes. Identification of T cell epitopes of LLO. J Immunol. 1991 May 15;146(10):3604–3616. [PubMed] [Google Scholar]
- Tarkkanen J., Saksela E., Lanier L. L. Bacterial activation of human natural killer cells. Characteristics of the activation process and identification of the effector cell. J Immunol. 1986 Oct 15;137(8):2428–2433. [PubMed] [Google Scholar]
- Timonen T., Saksela E. Isolation of human NK cells by density gradient centrifugation. J Immunol Methods. 1980;36(3-4):285–291. doi: 10.1016/0022-1759(80)90133-7. [DOI] [PubMed] [Google Scholar]
- West W. H., Cannon G. B., Kay H. D., Bonnard G. D., Herberman R. B. Natural cytotoxic reactivity of human lymphocytes against a myeloid cell line: characterization of effector cells. J Immunol. 1977 Jan;118(1):355–361. [PubMed] [Google Scholar]
- Wherry J. C., Schreiber R. D., Unanue E. R. Regulation of gamma interferon production by natural killer cells in scid mice: roles of tumor necrosis factor and bacterial stimuli. Infect Immun. 1991 May;59(5):1709–1715. doi: 10.1128/iai.59.5.1709-1715.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]