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. 1995 Aug;96(2):676–686. doi: 10.1172/JCI118110

The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense mechanism in mice against extraintestinally invasive Escherichia coli.

A Cross 1, L Asher 1, M Seguin 1, L Yuan 1, N Kelly 1, C Hammack 1, J Sadoff 1, P Gemski Jr 1
PMCID: PMC185248  PMID: 7635960

Abstract

Extraintestinally invasive Escherichia coli (EC) that possess both a complete LPS and K1 capsule evade both complement-mediated bacteriolysis and neutrophil-mediated killing. Since C3H/HeJ mice that are hyporesponsive to LPS were uniquely susceptible to lethal infection with EC of this phenotype, we speculated there was an LPS-initiated host defense mechanism against this pathogenic phenotype. The LPS-normoresponsive C3H/HeN as well as the C3H/HeJ mice cleared these EC from the circulation within 4 h of intravenous administration. Whereas electron micrographs of the liver demonstrated these EC undergoing degeneration within the phagolysosomes of of both macrophages and Kupffer cells of C3H/HeN mice, these EC replicated within these cells of the C3H/HeJ mice. Restoration of anti-EC activity of C3H/HeJ mice occurred with activation of Kupffer cells and peritoneal macrophages in vivo with BCG and in vitro with IFN-gamma, but not with LPS. Pretreatment of C3H/HeJ mice with a combination of recombinant murine IL-1 and TNF-alpha also restored the killing of K1(+)-EC but did not enhance the killing of a K1(-)-EC mutant. These data are consistent with the hypothesis that (a) there is no intrinsic inability of C3H/HeJ phagocytes to kill EC, but (b) an LPS-initiated, cytokine-mediated host defense mechanism is required for such killing. These studies emphasize the importance of bacterial surface characteristics in the interaction with specific host defenses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berkow R. L., Wang D., Larrick J. W., Dodson R. W., Howard T. H. Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor. J Immunol. 1987 Dec 1;139(11):3783–3791. [PubMed] [Google Scholar]
  2. Bortolussi R., Ferrieri P., Björkstén B., Quie P. G. Capsular K1 polysaccharide of Escherichia coli: relationship to virulence in newborn rats and resistance to phagocytosis. Infect Immun. 1979 Jul;25(1):293–298. doi: 10.1128/iai.25.1.293-298.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cavaillon J. M., Fitting C., Haeffner-Cavaillon N., Kirsch S. J., Warren H. S. Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide. Infect Immun. 1990 Jul;58(7):2375–2382. doi: 10.1128/iai.58.7.2375-2382.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cross A. S., Gemski P., Sadoff J. C., Orskov F., Orskov I. The importance of the K1 capsule in invasive infections caused by Escherichia coli. J Infect Dis. 1984 Feb;149(2):184–193. doi: 10.1093/infdis/149.2.184. [DOI] [PubMed] [Google Scholar]
  6. Cross A. S., Sadoff J. C., Kelly N., Bernton E., Gemski P. Pretreatment with recombinant murine tumor necrosis factor alpha/cachectin and murine interleukin 1 alpha protects mice from lethal bacterial infection. J Exp Med. 1989 Jun 1;169(6):2021–2027. doi: 10.1084/jem.169.6.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feingold D. S. The serum bactericidal reaction. IV. Phenotypic conversion of Escherichia coli from serum-resistance to serum-sensitivity by diphenylamine. J Infect Dis. 1969 Oct;120(4):437–444. doi: 10.1093/infdis/120.4.437. [DOI] [PubMed] [Google Scholar]
  8. Glynn A. A., Howard C. J. The sensitivity to complement of strains of Escherichia coli related to their K antigens. Immunology. 1970 Mar;18(3):331–346. [PMC free article] [PubMed] [Google Scholar]
  9. Green S. J., Mellouk S., Hoffman S. L., Meltzer M. S., Nacy C. A. Cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from L-arginine by macrophages and hepatocytes. Immunol Lett. 1990 Aug;25(1-3):15–19. doi: 10.1016/0165-2478(90)90083-3. [DOI] [PubMed] [Google Scholar]
  10. Howard C. J., Glynn A. A. The virulence for mice of strains of Escherichia coli related to the effects of K antigens on their resistance to phagocytosis and killing by complement. Immunology. 1971 May;20(5):767–777. [PMC free article] [PubMed] [Google Scholar]
  11. Hsueh W., Sun F. F., Henderson S. The biosynthesis of leukotriene B4, the predominant lipoxygenase product in rabbit alveolar macrophages, is enhanced during immune activation. Biochim Biophys Acta. 1985 Jun 14;835(1):92–97. [PubMed] [Google Scholar]
  12. Kim K. S., Itabashi H., Gemski P., Sadoff J., Warren R. L., Cross A. S. The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat. J Clin Invest. 1992 Sep;90(3):897–905. doi: 10.1172/JCI115965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kim K. S., Kang J. H., Cross A. S., Kaufman B., Zollinger W., Sadoff J. Functional activities of monoclonal antibodies to the O side chain of Escherichia coli lipopolysaccharides in vitro and in vivo. J Infect Dis. 1988 Jan;157(1):47–53. doi: 10.1093/infdis/157.1.47. [DOI] [PubMed] [Google Scholar]
  14. Kreger B. E., Craven D. E., Carling P. C., McCabe W. R. Gram-negative bacteremia. III. Reassessment of etiology, epidemiology and ecology in 612 patients. Am J Med. 1980 Mar;68(3):332–343. doi: 10.1016/0002-9343(80)90101-1. [DOI] [PubMed] [Google Scholar]
  15. Mancilla J., García P., Dinarello C. A. The interleukin-1 receptor antagonist can either reduce or enhance the lethality of Klebsiella pneumoniae sepsis in newborn rats. Infect Immun. 1993 Mar;61(3):926–932. doi: 10.1128/iai.61.3.926-932.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McCabe W. R., Kaijser B., Olling S., Uwaydah M., Hanson L. A. Escherichia coli in bacteremia: K and O antigens and serum sensitivity of strains from adults and neonates. J Infect Dis. 1978 Jul;138(1):33–41. doi: 10.1093/infdis/138.1.33. [DOI] [PubMed] [Google Scholar]
  17. Medearis D. N., Jr, Kenny J. F. Observations concerning the pathogenesis of E. coli infections in mice. J Immunol. 1968 Sep;101(3):534–540. [PubMed] [Google Scholar]
  18. Murray H. W. Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med. 1988 Apr;108(4):595–608. doi: 10.7326/0003-4819-108-4-595. [DOI] [PubMed] [Google Scholar]
  19. Nathan C. F. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest. 1987 Dec;80(6):1550–1560. doi: 10.1172/JCI113241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ohlsson K., Björk P., Bergenfeldt M., Hageman R., Thompson R. C. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990 Dec 6;348(6301):550–552. doi: 10.1038/348550a0. [DOI] [PubMed] [Google Scholar]
  21. Olling S. Sensitivity of gram-negative bacilli to the serum bactericidal activity: a marker of the host-parasite relationship in acute and persisting infections. Scand J Infect Dis Suppl. 1977;(10):1–40. doi: 10.3109/inf.1977.9.suppl-10.01. [DOI] [PubMed] [Google Scholar]
  22. Pelkonen S., Pluschke G. Recombinant interleukin-1 stimulates clearance of Escherichia coli K1 bacteraemia. Microb Pathog. 1989 Jun;6(6):415–424. doi: 10.1016/0882-4010(89)90083-1. [DOI] [PubMed] [Google Scholar]
  23. ROANTREE R. J., PAPPAS N. C. The survival of strains of enteric bacilli in the blood stream as related to their sensitivity to the bactericidal effect of serum. J Clin Invest. 1960 Jan;39:82–88. doi: 10.1172/JCI104031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. ROWLEY D. The virulence of strains of Bacterium coli for mice. Br J Exp Pathol. 1954 Dec;35(6):528–538. [PMC free article] [PubMed] [Google Scholar]
  25. Roantree R. J., Rantz L. A. A STUDY OF THE RELATIONSHIP OF THE NORMAL BACTERICIDAL ACTIVITY OF HUMAN SERUM TO BACTERIAL INFECTION. J Clin Invest. 1960 Jan;39(1):72–81. doi: 10.1172/JCI104029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roantree R. J. Salmonella O antigens and virulence. Annu Rev Microbiol. 1967;21:443–466. doi: 10.1146/annurev.mi.21.100167.002303. [DOI] [PubMed] [Google Scholar]
  27. Rowley D. Sensitivity of rough gram-negative bacteria to the bactericidal action of serum. J Bacteriol. 1968 May;95(5):1647–1650. doi: 10.1128/jb.95.5.1647-1650.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schlesinger L. S., Horwitz M. A. Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN-gamma activation inhibits complement receptor function and phagocytosis of this bacterium. J Immunol. 1991 Sep 15;147(6):1983–1994. [PubMed] [Google Scholar]
  29. Seguin M. C., Ballou W. R., Nacy C. A. Interactions of Plasmodium berghei sporozoites and murine Kupffer cells in vitro. J Immunol. 1989 Sep 1;143(5):1716–1722. [PubMed] [Google Scholar]
  30. Simoons-Smit A. M., Verwey-van Vught A. M., Kanis I. Y., MacLaren D. M. Virulence of Klebsiella strains in experimentally induced skin lesions in the mouse. J Med Microbiol. 1984 Feb;17(1):67–77. doi: 10.1099/00222615-17-1-67. [DOI] [PubMed] [Google Scholar]
  31. Stone R. Search for sepsis drugs goes on despite past failures. Science. 1994 Apr 15;264(5157):365–367. doi: 10.1126/science.8153620. [DOI] [PubMed] [Google Scholar]
  32. Tite J. P., Dougan G., Chatfield S. N. The involvement of tumor necrosis factor in immunity to Salmonella infection. J Immunol. 1991 Nov 1;147(9):3161–3164. [PubMed] [Google Scholar]
  33. Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  34. Vermeulen C., Cross A., Byrne W. R., Zollinger W. Quantitative relationship between capsular content and killing of K1-encapsulated Escherichia coli. Infect Immun. 1988 Oct;56(10):2723–2730. doi: 10.1128/iai.56.10.2723-2730.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wolberg G., DeWitt C. W. Mouse virulence of K(L) antigen-containing strains of Escherichia coli. J Bacteriol. 1969 Nov;100(2):730–737. doi: 10.1128/jb.100.2.730-737.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]

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