Summary:
The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared. Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine production assessed. All strains were potent inducers of IL1β, IL8, and TNFα production. Heat-killed bacteria induced consistently higher IL1β and TNFα production than did the cell-free bacterial supernatants (P<0.01). The strains did not induce any proliferative response, nor any significant TNFβ or IFNγ production. No difference in cytokine-inducing capacity could be detected between the cohorts of severe and nonsevere isolates. Comparison of strains causing severe and nonsevere episodes in the same patient (n=2) revealed a significantly higher induction of IL1β by the severe episodes associated isolates as compared to the nonsevere (P<0.04). The study underscores the importance of the host–pathogen interplay in determining the level of inflammation, and hence the severity of disease.
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References
Bochud PY, Eggiman P, Calandra T et al. Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis 1994; 18: 25–31.
Persson L, Vikerfors T, Sjoberg L et al. Increased incidence of bacteraemia due to viridans streptococci in an unselected population of patients with acute myeloid leukaemia. Scand J Infect Dis 2000; 32: 615–621.
Bochud PY, Calandra T, Francioli P . Bacteremia due to viridans streptococci in neutropenic patients: a review. Am J Med 1994; 97: 256–264.
Cohen J, Donnelly JP, Worsley AM et al. Septicaemia caused by viridans streptococci in neutropenic patients with leukaemia. Lancet 1983; 2: 1452–1454.
Razonable RR, Litzow MR, Khaliq Y et al. Bacteremia due to viridans group Streptococci with diminished susceptibility to Levofloxacin among neutropenic patients receiving levofloxacin prophylaxis. Clin Infect Dis 2002; 34: 1469–1474.
Belko J, Goldmann DA, Macone A et al. Clinically significant infections with organisms of the Streptococcus milleri group. Pediatr Infect Dis J 2002; 21: 715–723.
Murray HW, Gross KC, Masur H et al. Serious infections caused by Streptococcus milleri. Am J Med 1978; 64: 759–764.
Le Roy D, Morand P, Lengacher S et al. Streptococcus mitis cell walls and lipopolysaccharide induce lethality in D-galactosamine-sensitized mice by a tumor necrosis factor-dependent pathway. Infect Immun 1996; 64: 1846–1849.
Soto A, McWhinney PH, Kibbler CC et al. Cytokine release and mitogenic activity in the viridans streptococcal shock syndrome. Cytokine 1998; 10: 370–376.
Hanage WP, Cohen J . Stimulation of cytokine release and adhesion molecule expression by products of viridans streptococci. J Infect Dis 2002; 185: 357–367.
Hack CE, Hart M, van Schijndel RJ et al. Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun 1992; 60: 2835–2842.
Martin TR . Lung cytokines and ARDS: Roger S. Mitchell Lecture. Chest 1999; 116: 2S–8S.
Kilian M, Mikkelsen L, Henrichsen J . Taxonomic study of viridans streptococci: description of Streptoccoccus gordonii sp. nov. and emended descriptions of Streptococcus sanguis (White and Niven 1946), Streptococcus oralis (Bridge and Sneath 1982), and Streptococcus mitis (Andrewes and Horder 1906). Int J Syst Bacteriol 1989; 39: 471–484.
Hermans PW, Sluijter M, Hoogenboezem T et al. Comparative study of five different DNA fingerprint techniques for molecular typing of Streptococcus pneumoniae strains. J Clin Microbiol 1995; 33: 1606–1612.
Norrby-Teglund A, Kaul R, Low DE et al. Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigen-induced T cell proliferation and cytokine production. J Immunol 1996; 156: 3057–3064.
Andersson J, Nagy S, Bjork L et al. Bacterial toxin-induced cytokine production studied at the single-cell level. Immunol Rev 1992; 127: 69–96.
Engel A, Kern P, Kern WV . Levels of cytokines and cytokine inhibitors in the neutropenic patient with alpha-hemolytic streptococcus shock syndrome. Clin Infect Dis 1996; 23: 785–789.
Elting LS, Bodey GP, Keefe BH . Septicemia and shock syndrome due to viridans streptococci: a case–control study of predisposing factors. Clin Infect Dis 1992; 14: 1201–1207.
Sparrelid E, Hagglund H, Remberger M et al. Bacteraemia during the aplastic phase after allogeneic bone marrow transplantation is associated with early death from invasive fungal infection. Bone Marrow Transplant 1998; 22: 795–800.
Marron A, Carratala J, Gonzalez-Barca E et al. Serious complications of bacteremia caused by Viridans streptococci in neutropenic patients with cancer. Clin Infect Dis 2000; 31: 1126–1130.
Burden AD, Oppenheim BA, Crowther D et al. Viridans streptococcal bacteraemia in patients with haematological and solid malignancies. Eur J Cancer 1991; 27: 409–411.
Bone RC . A critical evaluation of new agents for the treatment of sepsis. JAMA 1991; 266: 1686–1691.
Casey LC, Balk RA, Bone RC . Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 1993; 119: 771–778.
Cohen J, Carlet J . INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med 1996; 24: 1431–1440.
Martin TR . Cytokines and the acute respiratory distress syndrome (ARDS): a question of balance [news; comment]. Nat Med 1997; 3: 272–273.
Kotb M . Bacterial pyrogenic exotoxins as superantigens. Clin Microbiol Rev 1995; 8: 411–426.
Heumann D, Barras C, Severin A et al. Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes. Infect Immun 1994; 62: 2715–2721.
English BK, Patrick CC, Orlicek SL et al. Lipoteichoic acid from viridans streptococci induces the production of tumor necrosis factor and nitric oxide by murine macrophages. J Infect Dis 1996; 174: 1348–1351.
Standiford TJ, Arenberg DA, Danforth JM et al. Lipoteichoic acid induces secretion of interleukin-8 from human blood monocytes: a cellular and molecular analysis. Infect Immun 1994; 62: 119–125.
Matsushita K, Fujimaki W, Kato H et al. Immunopathological activities of extracellular products of Streptococcus mitis, particularly a superantigenic fraction. Infect Immun 1995; 63: 785–793.
Medzhitov R, Janeway C . Innate immunity. N Engl J Med 2000; 343: 338–344.
Ozinsky A, Underhill DM, Fontenot JD et al. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 2000; 97: 13766–13771.
Takeuchi O, Kawai T, Muhlradt PF et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 2001; 13: 933–940.
Vernier A, Diab M, Soell M et al. Cytokine production by human epithelial and endothelial cells following exposure to oral viridans streptococci involves lectin interactions between bacteria and cell surface receptors. Infect Immun 1996; 64: 3016–3022.
Acknowledgements
This work was supported by grants awarded by the Swedish Foundation for Strategic Research, Children's Cancer Foundation (1996/079 to ES, 2001/012 to MR, and 1999/004 to JA), grants from the Swedish Cancer Foundation (to OR), the Karolinska Institutet (to AN-T) and the Swedish Medical Research Council (012610 to AN-T and 10850 to JA), and Tobias Foundation (to AN-T). This study was conducted in accordance with guidelines for human experimentation as specified by the Ethical committee at Huddinge University Hospital, Stockholm, Sweden.
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Ihendyane, N., Sparrelid, E., Wretlind, B. et al. Viridans streptococcal septicaemia in neutropenic patients: role of proinflammatory cytokines. Bone Marrow Transplant 33, 79–85 (2004). https://doi.org/10.1038/sj.bmt.1704302
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DOI: https://doi.org/10.1038/sj.bmt.1704302