Abstract
Monocytes having phagocytosed mycobacteria are known to present the bacterial 65-kD heat shock protein (hsp) on their cell surface to alpha beta and gamma delta T lymphocytes. Cytotoxic CD4+ cells may then lyse monocytes expressing mycobacterial 65-kD hsp. However, it is not known whether 65-kD hsp directly stimulates monocyte functions other than antigen presentation. This study has demonstrated that following extraction of bacterial lipopolysaccharide, purified recombinant mycobacterial 65-kD hsp may directly activate THP-1 cells, a human monocytic line, to accumulate mRNA for and secrete tumour necrosis factor (TNF), a cytokine important in granuloma formation, the characteristic host immune response to mycobacterial infection. TNF gene expression and secretion following stimulation by hsp was dose-dependent and abolished by heat-induced proteolysis. Subsequently, THP-1 cells secreted IL-6 and IL-8, cytokines involved in recruitment and differentiation of T lymphocytes. The data indicate that secretion of proinflammatory cytokines from monocytes activated by mycobacterial 65-kD hsp may be important in the host immune response and in the development of antigen-specific T cell-mediated immunity.
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- Aarden L. A., De Groot E. R., Schaap O. L., Lansdorp P. M. Production of hybridoma growth factor by human monocytes. Eur J Immunol. 1987 Oct;17(10):1411–1416. doi: 10.1002/eji.1830171004. [DOI] [PubMed] [Google Scholar]
- Amiri P., Locksley R. M., Parslow T. G., Sadick M., Rector E., Ritter D., McKerrow J. H. Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature. 1992 Apr 16;356(6370):604–607. doi: 10.1038/356604a0. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Chensue S. W., Otterness I. G., Higashi G. I., Forsch C. S., Kunkel S. L. Monokine production by hypersensitivity (Schistosoma mansoni egg) and foreign body (Sephadex bead)-type granuloma macrophages. Evidence for sequential production of IL-1 and tumor necrosis factor. J Immunol. 1989 Feb 15;142(4):1281–1286. [PubMed] [Google Scholar]
- Christman M. F., Morgan R. W., Jacobson F. S., Ames B. N. Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium. Cell. 1985 Jul;41(3):753–762. doi: 10.1016/s0092-8674(85)80056-8. [DOI] [PubMed] [Google Scholar]
- Cohen I. R., Young D. B. Autoimmunity, microbial immunity and the immunological homunculus. Immunol Today. 1991 Apr;12(4):105–110. doi: 10.1016/0167-5699(91)90093-9. [DOI] [PubMed] [Google Scholar]
- Coulie P. G., Stevens M., Van Snick J. High- and low-affinity receptors for murine interleukin 6. Distinct distribution on B and T cells. Eur J Immunol. 1989 Nov;19(11):2107–2114. doi: 10.1002/eji.1830191121. [DOI] [PubMed] [Google Scholar]
- DeForge L. E., Remick D. G. Kinetics of TNF, IL-6, and IL-8 gene expression in LPS-stimulated human whole blood. Biochem Biophys Res Commun. 1991 Jan 15;174(1):18–24. doi: 10.1016/0006-291x(91)90478-p. [DOI] [PubMed] [Google Scholar]
- DeForge L. E., Remick D. G. Sandwich ELISA for detection of picogram quantities of interleukin-8. Immunol Invest. 1991 Feb;20(1):89–97. doi: 10.3109/08820139109054928. [DOI] [PubMed] [Google Scholar]
- Espevik T., Nissen-Meyer J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods. 1986 Dec 4;95(1):99–105. doi: 10.1016/0022-1759(86)90322-4. [DOI] [PubMed] [Google Scholar]
- Flesch I. E., Kaufmann S. H. Activation of tuberculostatic macrophage functions by gamma interferon, interleukin-4, and tumor necrosis factor. Infect Immun. 1990 Aug;58(8):2675–2677. doi: 10.1128/iai.58.8.2675-2677.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flesch I. E., Kaufmann S. H. Stimulation of antibacterial macrophage activities by B-cell stimulatory factor 2 (interleukin-6). Infect Immun. 1990 Jan;58(1):269–271. doi: 10.1128/iai.58.1.269-271.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friedland J. S., Remick D. G., Shattock R., Griffin G. E. Secretion of interleukin-8 following phagocytosis of Mycobacterium tuberculosis by human monocyte cell lines. Eur J Immunol. 1992 Jun;22(6):1373–1378. doi: 10.1002/eji.1830220607. [DOI] [PubMed] [Google Scholar]
- Friedland J. S., Suputtamongkol Y., Remick D. G., Chaowagul W., Strieter R. M., Kunkel S. L., White N. J., Griffin G. E. Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection. Infect Immun. 1992 Jun;60(6):2402–2408. doi: 10.1128/iai.60.6.2402-2408.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haregewoin A., Soman G., Hom R. C., Finberg R. W. Human gamma delta+ T cells respond to mycobacterial heat-shock protein. Nature. 1989 Jul 27;340(6231):309–312. doi: 10.1038/340309a0. [DOI] [PubMed] [Google Scholar]
- Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
- Havell E. A. Evidence that tumor necrosis factor has an important role in antibacterial resistance. J Immunol. 1989 Nov 1;143(9):2894–2899. [PubMed] [Google Scholar]
- Houssiau F. A., Coulie P. G., Van Snick J. Distinct roles of IL-1 and IL-6 in human T cell activation. J Immunol. 1989 Oct 15;143(8):2520–2524. [PubMed] [Google Scholar]
- Kindler V., Sappino A. P., Grau G. E., Piguet P. F., Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989 Mar 10;56(5):731–740. doi: 10.1016/0092-8674(89)90676-4. [DOI] [PubMed] [Google Scholar]
- Koga T., Wand-Württenberger A., DeBruyn J., Munk M. E., Schoel B., Kaufmann S. H. T cells against a bacterial heat shock protein recognize stressed macrophages. Science. 1989 Sep 8;245(4922):1112–1115. doi: 10.1126/science.2788923. [DOI] [PubMed] [Google Scholar]
- Kunkel S. L., Spengler M., May M. A., Spengler R., Larrick J., Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380–5384. [PubMed] [Google Scholar]
- Lamb F. I., Kingston A. E., Estrada I., Colston M. J. Heterologous expression of the 65-kilodalton antigen of Mycobacterium leprae and murine T-cell responses to the gene product. Infect Immun. 1988 May;56(5):1237–1241. doi: 10.1128/iai.56.5.1237-1241.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larsen C. G., Anderson A. O., Appella E., Oppenheim J. J., Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989 Mar 17;243(4897):1464–1466. doi: 10.1126/science.2648569. [DOI] [PubMed] [Google Scholar]
- Liew F. Y., Li Y., Millott S. Tumour necrosis factor (TNF-alpha) in leishmaniasis. II. TNF-alpha-induced macrophage leishmanicidal activity is mediated by nitric oxide from L-arginine. Immunology. 1990 Dec;71(4):556–559. [PMC free article] [PubMed] [Google Scholar]
- Lotz M., Jirik F., Kabouridis P., Tsoukas C., Hirano T., Kishimoto T., Carson D. A. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988 Mar 1;167(3):1253–1258. doi: 10.1084/jem.167.3.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moreno C., Taverne J., Mehlert A., Bate C. A., Brealey R. J., Meager A., Rook G. A., Playfair J. H. Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and murine macrophages. Clin Exp Immunol. 1989 May;76(2):240–245. [PMC free article] [PubMed] [Google Scholar]
- Orme I. M., Miller E. S., Roberts A. D., Furney S. K., Griffin J. P., Dobos K. M., Chi D., Rivoire B., Brennan P. J. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens. J Immunol. 1992 Jan 1;148(1):189–196. [PubMed] [Google Scholar]
- Ottenhoff T. H., Ab B. K., Van Embden J. D., Thole J. E., Kiessling R. The recombinant 65-kD heat shock protein of Mycobacterium bovis Bacillus Calmette-Guerin/M. tuberculosis is a target molecule for CD4+ cytotoxic T lymphocytes that lyse human monocytes. J Exp Med. 1988 Nov 1;168(5):1947–1952. doi: 10.1084/jem.168.5.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rook G. A., Taverne J., Leveton C., Steele J. The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis. Immunology. 1987 Oct;62(2):229–234. [PMC free article] [PubMed] [Google Scholar]
- Shinnick T. M., Sweetser D., Thole J., van Embden J., Young R. A. The etiologic agents of leprosy and tuberculosis share an immunoreactive protein antigen with the vaccine strain Mycobacterium bovis BCG. Infect Immun. 1987 Aug;55(8):1932–1935. doi: 10.1128/iai.55.8.1932-1935.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsuchiya S., Yamabe M., Yamaguchi Y., Kobayashi Y., Konno T., Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980 Aug;26(2):171–176. doi: 10.1002/ijc.2910260208. [DOI] [PubMed] [Google Scholar]
- Ulich T. R., Guo K. Z., Remick D., del Castillo J., Yin S. M. Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6. J Immunol. 1991 Apr 1;146(7):2316–2323. [PubMed] [Google Scholar]
- Wahl S. M., Allen J. B., Dougherty S., Evequoz V., Pluznik D. H., Wilder R. L., Hand A. R., Wahl L. M. T lymphocyte-dependent evolution of bacterial cell wall-induced hepatic granulomas. J Immunol. 1986 Oct 1;137(7):2199–2209. [PubMed] [Google Scholar]
- Wallis R. S., Fujiwara H., Ellner J. J. Direct stimulation of monocyte release of interleukin 1 by mycobacterial protein antigens. J Immunol. 1986 Jan;136(1):193–196. [PubMed] [Google Scholar]

