Abstract
Invasive microorganisms encounter defensive attempts of the host to starve, destroy and eliminate the infection. In experimental model systems aiming to imitate defensive actions of the host, microorganisms respond by the rapid acceleration in the rate of expression of heat shock and other stress proteins. Heat shock proteins (hsp) of most if not all pathogens are major immune targets for both B- and T-cells. Host cells involved in the defensive action cannot avoid exposure to their own reactive compounds, such as oxygen radicals, resulting in premature cell death and tissue damage. Long-term consequences to the host may include cancer. In cells in tissue culture, induction of host-specific hsps occurs upon exposure to oxidants and in viral infections. Drugs that bind to members of the hsp70 family induce peroxisome proliferation and hepatocarcinoma, but may open the way for the development of novel drugs in support of antimetabolite treatment of infections and cancer.
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Literatur
Aarstad, H. J., Thiele, D., and Seljelid, R., The effect of various contexts of stress on the mouse spleen lymphocytes and macrophage co-stimulatory activity. Scand. J. Immun.33 (1991) 461–472.
Alvares, K., Carrillo, A., Yuan, P. M., Kawano, H., Morimoto, R. I., and Reddy, J. K., Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein Hsp70 family. Proc. natl Acad. Sci. USA87 (1990) 5293–5297.
Ames, B. N., Dietary carcinogens and anticarcinogens. Science221 (1983) 1256–1264.
Ames, B. N., and Gold, L. S., Chemical carcinogenesis: Too many rodent carcinogens. Proc. natl Acad. Sci. USA87 (1990) 7772–7776.
Babior, B. M., Oxidants from phagocytes: agents of defense and destruction. Blood64 (1984) 959–966.
Breton-Gorius, J., Mason, D. Y., Buriot, D., Vilde, J. L., and Griscelli, C., Lactoferrin deficiency as a consequence of a lack of specific granules in neutrophils from a patient with recurrent infections. Am. J. Path.99 (1980) 413–419.
Buchmeier, N. A., and Heffron, F., Induction ofSalmonella stress protein upon infection of macrophages. Science248 (1990) 730–732.
Chance, B., Sies, H., and Boveris, A., Hydroperoxide metabolism in mammalian organs. Physiol. Rev.59 (1979) 527–605.
Christman, M. F., Morgan, R. W., Jacobson, F. S., and Ames, B. N., Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins inSalmonella typhimurium. Cell41 (1985) 753–762.
Cohen, I. R., and Young, D. B., The immune system's view of invading microorganisms, autoimmunity and the immunological homunculus. Immun. Today12 (1991) 105–110.
Cohen, S. S., and Barner, H. D., Studies on unbalanced growth inEscherichia coli. Proc. natl Acad. Sci. USA40 (1955) 885–893.
Collins, P. L., and Hightower, L. E., Newcastle disease virus stimulates the cellular accumulation of stress (heat shock) mRNAs and proteins. J. Virol.44 (1982) 703–707.
Donati, Y. R. A., Slosman, D. O., and Polla, B. S., Oxidative injury and heat shock response. Biochem. Pharmac.40 (1990).
Drahos, D. J., and Hendrix, R. W., Effect of bacteriophage lambda infection on synthesis of GroE protein and otherEscherichia coli proteins. J. Bact.149 (1982) 1050–1063.
Duesberg, P. H., Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation. Proc. natl Acad. Sci. USA86 (1989) 755–764.
Elion, G. B., The purine path to chemotherapy. Science244 (1989) 41–47.
Flesch, I. E. A., and Kaufman, S. H. E., Attempts to characterize the mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages. Infect. Immun.56 (1988) 1464–1469.
Flesch, I. E. A., and Kaufman, S. H. E., Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates. Infect. Immun.59 (1991) 3213–3218.
Forman, H. J., and Thomas, M. J., Oxidant production and bactericidal activity of phagocytes. A. Rev. Physiol.48 (1986) 669–680.
Fraga, C. G., Shigenaga, M. K., Park, J.-W., Degan, P., and Ames, B. N., Oxidative damage of DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc. natl Acad. Sci. USA87 (1990) 4533–4537.
Hoiseth, S. K., and Stocker, B. A. D., Aromatic-dependentSalmonella typhimurium are non virulent and effective as live vaccines. Nature291 (1981) 238–239.
Irving, W., Donnelly, P., and Starke, I., Infection and the Immunocompromised Patient. Ed. A. Geddes. Current Medical Literature Ltd, London 1985.
Ivins, B. E., Welkos, S. L., Knudson, G. B., and Little, S. F., Immunization against anthrax with aromatic compound-dependent (Aro−) mutants ofBacillus anthracis and with recombinant strains ofBacillus subtilis that produce anthrax protective antigen. Infect. Immun.58 (1990) 303–309.
Iyer, G. Y. N., Islam, D. M. F., and Quastel, J. H., Biochemical aspects of phagocytosis. Nature192 (1961) 535–545.
Kaufmann, S. H. E., Vath, U., Thole, J. E. R., Van Embden, J. D. A., and Emmrich, F., Enumeration of T cells reactive withMycobacterium tuberculosis organisms and specific for the recombinant 64 kDa protein. Eur. J. Immun.17 (1987) 351–357.
Kaufmann, S. H. E., Immunity against intracellular bacteria: Biological effector functions and antigen specificity of T lymphocytes. Curr. Topics Microbiol. Immun.138 (1988) 141–176.
Khandjian, E. W., and Türler, H., Simian virus 40 and Polyoma virus induce synthesis of heat shock proteins in permissive cells. Molec. cell. Biol.3 (1983) 1–8.
Kochan, J., and Murialdo, H., Stimulation of GroE synthesis inEscherichia coli by bacteriophage lambda infection. J. Bact.149 (1982) 1166–1170).
Kornberg, A., DNA Replication. W. H. Freeman and Company, San Francisco 1980.
Kyprianou, N., and Isaacs, J. T., ‘Thymineless’ death in androgen-independent prostatic cancer cells. Biochem. biophys. Res. Commun.165 (1989) 73–81.
Lamb, J. R., Ivanyi, J., Rees, A. D. M., Rothbard, J. B., Howland, K., Young, R. A., and Young, D. B., Mapping of T cell epitopes using recombinant antigens and synthetic peptides. EMBO J.6 (1987) 1245–1249.
LaThangue, N. B., Shriver, K., Dawson, C., and Chan, W. L., Herpes simplex virus infection causes the accumulation of a heat shock protein. EMBO J.3 (1984) 267–277.
Loeb, L. A., Endogenous carcinogenesis: Molecular oncology into the twenty-first century. Cancer Res.49 (1989) 5489–5496.
Matin, A., The molecular basis of carbon-starvation-induced general resistance inEscherichia coli. Molec. Microbiol.5 (1991) 3–10.
McClarty, G. A., Chan, A. K., Choy, B. K., and Wright, J. A., Increased ferritin gene expression is associated with increased ribonucleotide reductase gene expression and the establishment of hydroxyurea resistance in mammalian cells. J. biol. Chem.265 (1990) 7539–7547.
Mims, C. A., The Pathogenesis of Infectious Disease, 3rd ed. Academic Press, London 1987.
Morgan, R. W., Christman, M. F., Jacobson, F. S., Storz, G., and Ames, B. N., Hydrogen peroxide-inducible proteins inSalmonella typhimurium overlap with heat shock and other stress proteins. Proc. natl Acad. Sci. USA83 (1986) 8059–8063.
Morimoto, R. I., Tissières, A., and Georgopoulos, C., The stress response, function of proteins, and perspectives, in: Stress Proteins in Biology and Medicine, pp. 1–36. Eds R. I. Morimoto, A. Tissières and C. Georgopoulos. Cold Spring Harbor Laboratory Press 1990.
Neilands, J. B., Siderophores: diverse roles in microbial and human physiology, in: Iron Metabolism, pp. 107–124. Ciba Foundation Symposia 52 (new series). Elsevier, Amsterdam 1977.
Nevins, J. R., Induction of the synthesis of a 70,000 Dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell29 (1982) 913–919.
O'Callaghan, D., Maskell, D., Liew, F. Y., Easmon, C. S. F., and Dougan, G., Characterization of aromatic- and purine-dependentSalmonella typhimurium: attenuation, persistence, and ability to induce protective immunity in BALB/c mice. Infect. Immun.56 (1988) 419–423.
Oda, T., Akaike, T., Hamamoto, T., Suzuki, F., Hirano, T., and Maeda, H., Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD. Science244 (1989) 974–976.
Peterson, P. K., Chao, C. C., Molitor, T., Murtaugh, M., Strgar, F., and Sharp, B. M., Stress and pathogenesis of infectious disease. Rev. infect. Dis.13 (1991) 710–720.
Polla, B. S., Bonventre, J. V., and Krane, S. M., 1,25-Dihydroxyvitamin D3 increases the toxicity of hydrogen peroxide in the human monocytic line U937: the role of calcium and heat shock. J. Cell Biol.107 (1988) 373–380.
Polla, B. S., Healy, A. M., Wojno, W. C., and Krane, S. M., Hormone 1α,25-dihydroxyvitamin D3 modulates heat shock response in monocytes. Am. J. Physiol.252 (1987) C640-C649.
Polla, B. S., and Kantengwa, S., Heat shock proteins and inflammation, in: Current Topics in Microbiological Immunology, vol. 167 pp. 92–105. Ed. S. H. E. Kaufmann. Springer Verlag, Berlin 1991.
Preston-Martin, S., Pike, M. C., Ross, R. K., Jones, P. A., and Henderson, B. E., Increased cell division as a cause of human cancer. Cancer Res.50 (1990) 7415–7421.
Pryor, W. A., Oxy-radicals and related species: Their formation, life-times, and reactions. A. Rev. Physiol.48 (1986) 657–667.
Rénia, L., Mattei, D., Goma, J., Pied, S., Dubois, P., Miltgen, F., Nüssler, A., Matile, H., Menégaux, F., Gentilini, M., and Mazier, D., A malaria heat-shock-like determinant expressed on the infected hepatocyte surface is the target of antibody-dependent cell-mediated cytotoxic mechanisms by nonparenchymal liver cells. Eur. J. Immun.20 (1990) 1445–1449.
Rolfe, R., On the mechanism of thymineless death inBacillus subtilis. Proc. natl Acad. Sci. USA57 (1967) 114–121.
Salin, M. L., and McCord, J. M., Superoxide dismutases in polymorphonuclear leucocytes. J. clin. Invest.54 (1974) 1005–1009.
Salin, M. L., and McCord, J. M., Free radicals and inflammation: protection of phagocytosing leukocytes by superoxide dismutase. J. clin. Invest.56 (1975) 1319–1323.
Shinnick, T. M., Heat shock proteins as antigens of bacterial and parasitic pathogens, in: Current Topics in Microbiological Immunology, vol. 167, pp. 145–160. Ed. S. H. E. Kaufmann. Springer Verlag, Berlin 1991.
Sokolovic, Z., Fuchs, A., and Goebel, W., Synthesis of species-specific proteins by virulent strains ofListeria monocytogenes. Infect. Immun.58 (1990) 3582–3587.
Spitznagel, J. K., Constitutive defences of the body, in: Mechanisms of Microbial Disease, pp. 68–93. Eds M. Schaechter, G. Medoff and D. Schlessinger. Williams & Wilkins, Baltimore 1989.
Styblo, K., Overview and epidemiologic assessment of the current global tuberculosis situation with an emphasis on control in developing countries. Rev. infect. Dis.11, Suppl. 2 (1989) S339-S346.
Subjeck, J. R., and Shyy, T.-T., Stress protein systems of mammalian cells. Am. J. Physiol.250 (1986) C1-C17.
Themel, K. G., and Lüders, C. J., Die Bedeutung tuberkulöser Narben für die Entstehung des peripheren Lungenkarzinoms: Ein Beitrag zum Krankheitsbild des Lungennarbenkrebses. Dt. med. Wschr.80 (1955) 1360–1363.
Thole, J. E. R., van Schooten, W. C. A., Keulen, W. J., Hermans, P. W. M., Janson, A. A. M., de Fries, R. R. P., Kolk, A. H. J., and van Embden, J. D. A., Use of recombinant antigens expressed inEscherichia coli K-12 to map B cell and T cell epitopes on the immunodominant 65 kDa protein ofMycobacterium bovis BCG. Infect. Immun.56 (1988) 1633–1640.
Tong, C., Fazio, M., and Williams, G. M., Cell cycle-specific mutagenesis at the hypoxanthine phosphoribosyltransferase locus in adult rat liver epithelial cells. Proc. natl Acad. Sci. USA77 (1980) 7377–7379.
VanBogelen, R. A., Kelley, P. M., and Neidhart, F. C., Differential induction of heat shock, SOS, and oxidation stress regulons and accumulation of nucleotides inEscherichia coli. J. Bact.169 (1987) 26–32.
Weinberg, E. D., Iron withholding: a defense against infection and neoplasia. Physiol. Rev.64 (1984) 65–102.
Woods, D. D., The biochemical mode of action of the sulfonamide drugs. J. gen. Microbiol.29 (1962) 687–702.
Yin, H. L., and Stossel, T. P., The mechanism of phagocytosis, in: Phagocytosis, Past and Future, pp. 12–27. Eds M. Karnovsky and L. Bolis. Academic Press, New York 1982.
Young, D. B., Stress proteins as antigens during infection, in: Stress Proteins in Inflammation, pp. 155–168. Eds R. Burdon, C. Rice-Evans, D. Blake and V. Winrow, Richelieu Press, London 1990.
Young, D. B., Lathigra, R., Hendrix, R., Sweetser, D., and Young, R. A., Stress proteins are immune targets in leprosy and tuberculosis. Proc. natl Acad. Sci. USA85 (1988) 4267–4270.
Young, D., Garbe, T., Lathigra, R., and Abou-Zeid, C., Protein antigens: structure, function and regulation, in: Molecular Biology of the Mycobacteria, pp. 1–35. Ed. J.-J. McFadden. Surrey University Press, Guildford 1990.
Young, D. B., Mehlert, A., and Smith, D. F., Stress proteins and infectious diseases, in: Stress Proteins in Biology and Medicine, pp. 131–165. Eds R. Morimoto, A. Tissières and C. Georgopoulos. Cold Spring Harbor Laboratory Press 1990.
Young, D. B., and Garbe, T. R., Heat shock proteins and antigens ofMycobacterium tuberculosis. Infect. Immun.59 (1991) 3086–3093.
Ziegler, H. K., Induced defenses of the body, in: Mechanisms of Microbial Disease, pp. 68–93. Eds M. Schaechter, G. Medoff and D. Schlessinger. Williams & Wilkins, Baltimore 1989.
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Garbe, T.R. Heat shock proteins and infection: Interactions of pathogen and host. Experientia 48, 635–639 (1992). https://doi.org/10.1007/BF02118308
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DOI: https://doi.org/10.1007/BF02118308