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Infection

, Volume 13, Supplement 2, pp S171–S176 | Cite as

Genetic factors in host resistance to urinary tract infection

  • Catharina Svanborg Edén
  • L. Hagberg
  • D. Briles
  • J. McGhee
  • S. Michalec
Article

Summary

In patients with recurrent pyelonephritis, the pathogenetic events proceed through intestinal colonization, spread to the urinary tract and persistence, seemingly uninterrupted by host defense mechanisms. The factors responsible for the deficient bacterial clearance from the kidneys of these patients, and the genetic control, have not been identified. The susceptibility to colonization has been linked to an increased receptivity for attaching bacteria of the uroepithelia, and to an overrepresentation of the P1 blood group phenotype. To evaluate the role of defects in host defense for the susceptibility to pyelonephritis, experimental UTI in mouse strains with known deficiencies was used. A highly significant increase in susceptibility was noted for C3H/HeJ compared to C3H/HeN mice. The bacterial recovery was inversely correlated to the mitogenic response to LPS. Back-cross analysis revealed a linkage of susceptibility to theLps d /Lps d genotype. In contrast, T and B lymphocyte and complement (C5) defects had little effect on the clearance ofEscherichia coli from the kidneys. It is concluded that the inflammatory mechanisms induced by LPS are essential for resistance to experimental pyelonephritis.

Keywords

Pyelonephritis Bacterial Clearance Intestinal Colonization ofEscherichia Coli Pathogenetic Event 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Genetische Faktoren der körpereigenen Abwehr gegen Harnwegsinfektionen

Zusammenfassung

Bei Patienten mit rezidivierender Pyelonephritis schreiten die pathogenen Vorgänge offensichtlich ohne Unterbrechung durch körpereigene Abwehrmechanismen fort von der Besiedelung des Darmes bis zur Ausbreitung der Erreger im Harntrakt und ihrer Persistenz. Bislang ist nicht bekannt, welche Faktoren für die fehlende Bakterien-Clearance aus den Nieren bei diesen Patienten verantwortlich sind und wie sie genetisch kontrolliert werden. Die Empfänglichkeit für Kolonisation ist mit einer erhöhten Anheftbarkeit von Bakterien an den uroepithelialen Zellen verbunden, dabei ist der Blutgruppen-Phänotyp P1 überstark repräsentiert. Anhand der experimentellen Harnwegsinfektion bei Mäusestämmen mit bekannten Immundefekten wurde die Bedeutung von Abwehrstörungen für die Empfänglichkeit für Pyelonephritis untersucht. Bei C3H/HeJ-Mäusen war eine im Vergleich zu C3H/HeN-Mäusen signifikant erhöhte Empfänglichkeit für Harnwegsinfektionen festzustellen. Die Bakterienwiederfindungs-rate stand in umgekehrter Beziehung zur mitogenen Antwort auf LPS. Durch Rückkreuzungsanalyse ließ sich eine Verbindung der Empfänglichkeit mit demLps d /Lps d Genotyp nachweisen. T- und B-Lymphozyten und Komplement (C5)-Defekte hatten auf die Clearance vonEscherichia coli aus den Nieren wenig Einfluß. Daraus ist zu schließen, daß die durch LPS induzierten entzündlichen Vorgänge für die Widerstandsfähigkeit gegen experimentelle Pyelonephritis unbedingt nötig sind.

Literature

  1. 1.
    Svanborg Edén, C., Fasth, A., Jodal, U. Immunology of urinary tract infections. In:Reeves, D. S., Geddes, A. M., (eds.): Recent advances in infection. Churchill Livingstone, New York 1982, pp. 141–162.Google Scholar
  2. 2.
    Jodal, U., Ahlstedt, S., Carlsson, B., Hanson, L. Å., Lindberg, U., Sohl Åkerlund, A. Local antibodies in childhood urinary tract infection. Int. Arch. Allergy 47 (1974) 537–546.Google Scholar
  3. 3.
    Caugant, D., Lidin-Janson, G., Lindberg, U., Svanborg Edén, C.: Intestinal carriage ofE. coli strains causing urinary tract infection. J. Infect. Dis. (1984) (In print).Google Scholar
  4. 4.
    Lidin Janson, G., Hanson, L. Å., Kaijser, B., Lincoln, K., Lindberg, U., Olling, S., Wedel, H. Comparison ofE. coli from bacteriuric patients with those from feces of healthy schoolchildren. J. Infect. Dis. 136 (1977) 346–353.Google Scholar
  5. 5.
    Fowler, J. E., Stamey, T. A. Studies of introital colonization in women with recurrent urinary tract infections. VII. The role of bacterial adherence. J. Urol. 117 (1977) 472–476.Google Scholar
  6. 6.
    Källenius, G., Winberg, J. Bacterial adherence to periurethral epithelial cells in girls prone to urinary tract infections. Lancet II (1978) 540.Google Scholar
  7. 7.
    Svanborg Edén, C., Jodal, U. Attachment ofEscherichia coli to sediment epithelial cells from UTI prone and healthy children. Infect. Immun. 26 (1979) 837–840.Google Scholar
  8. 8.
    Lomberg, H., Hanson, L. Å., Jacobsson, U., Jodal, U., Leffler, H., Svanborg Edén, C. P blood group phenotype, vesicoureteric reflux and the susceptibility to recurrent pyelonephritis. N. Engl. J. Med. 308 (1983) 1189–1192.Google Scholar
  9. 9.
    Kerr, D. N. S., PiNai, P. M. Identical twins with identical vesicoureteric reflux: chronic pyelonephritis in one. Br. Med. J. 256 (1983) 1245–1246.Google Scholar
  10. 10.
    Marcus, D. M., Kundu, S. K., Suzuki, A. The P blood group system: Recent progress in immunochemistry and genetics. Semin. Hematol. 18 (1981) 63–71.Google Scholar
  11. 11.
    Leffler, H., Svanborg Edén, C. Chemical identification of a glycosphingolipid receptor forEscherichia coli attaching to human urinary tract epithelial cells and agglutinating human erythrocytes. FEMS Microbiol. Lett. 8 (1980) 127–134.Google Scholar
  12. 12.
    Källenius, G., Möllby, R., Svenson, S. B., Winberg, J., Lundblad, A., Svensson, S. The pk antigen as receptor of pyelonephriticE. coli. FEMS Microbiol. Lett. 7 (1980) 297–302.Google Scholar
  13. 13.
    Lomberg, H., Jodal, U., Svanborg Edén, C., Leffler, H., Samuelsson, B. P1 blood group and urinary tract infection. Lancet I (1981) 551–552.Google Scholar
  14. 14.
    Hagberg, L., Engberg, I., Freter, R., Lam, J., Olling, S., Svanborg Edén, C. Ascending unobstructed urinary tract infection in mice caused by pyelonephritogenicE. coli of human origin. Infect. Immun. 40 (1983) 273–283.Google Scholar
  15. 15.
    Hagberg, L., Hull, R., Hull, S., Falkow, S., Freter, R., Svanborg Edén, C. Contribution of adhesion to bacterial persistence in the mouse urinary tract. Infect. Immun. 40 (1983) 265–272.Google Scholar
  16. 16.
    Amsbaugh, D. F., Hansen, C. T., Prescott, B., Stashak, P. W., Barthold, D. R., Baker, P. J. Genetic control of the antibody response to Type III pneumococcal polysaccharide in mice. I. Evidence that an X-linked gene plays a decisive role in determining responsiveness. J. Exp. Med. 136 (1972) 931–949.Google Scholar
  17. 17.
    Briles, D. E., Nahm, M., Schroer, K., Davie, J., Baker, P., Kearney, J., Barletta, R. antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3Streptococcus pneumoniae. J. Exp. Med. 153 (1981) 694–705.Google Scholar
  18. 18.
    Stevenson, M. M., Kongshavn, P. A. L., Skamene, E. Genetic linkage of resistance toListeria monocytogenes with macrophage inflammatory responses. J. Immunol. 127 (1981) 402–411.Google Scholar
  19. 19.
    O'Brien, A. D., Scher, D. L. I., Campbell, G. H., MacDermott, R. P., Formal, S. B. Genetic control of susceptibility toSalmonella typhimurium in mice: Role of the lps gene. J. Immunol. 124 (1980) 20–24.Google Scholar
  20. 20.
    Sultzer, B. M. Genetic control of leucocyte responses to endotoxin. Nature 219 (1968) 1253–1254.Google Scholar
  21. 21.
    Watson, J., Riblet, R. Genetic control of responses to bacterial lipopolysaccharides I. Evidence for a single gene that influences mitogenic and immunogenic responses to lipopolysaccharides. J. Exp. Med. 140 (1974) 1147–1161.Google Scholar
  22. 22.
    Michalec, S. M., Kiyono, H., Babb, J. L., McGhee, J. R. Inheritance of lps nonresponsiveness and elevated splenic IgA immune responses in mice orally immunized with heterologous erythrocytes. J. Immunol. 125 (1980) 2220–2224.Google Scholar
  23. 23.
    Vogel, S. N., Hansen, C. T., Rosenstreich, D. L. Characterization of a congenitally LPS-resistant, athymic mouse strain. J. Immunol. 122 (1979) 619–622.Google Scholar
  24. 24.
    Watson, J., Riblet, R., Taylor, B. A. The response of recombinant inbred strains of mice to bacterial lipopolysaccharides. J. Immunol. 118 (1977) 2088–2093.Google Scholar
  25. 25.
    Plant, J., Glynn, A. A. Locating Salmonella resistance gene on mouse chromosome 1. Clin. Exp. Immunol. 37 (1979) 1–6.Google Scholar
  26. 26.
    O'Brien, A. D., Scher, I., Campbell, G. H., MacDermott, R. P., Formal, S. B. Susceptibility of CBA/N mice to infection withSalmonella typhimurium influence of the X-linked gene controlling B-lymphocyte function. J. Immunol. 123 (1979) 720–724.Google Scholar
  27. 27.
    Eisenstein, T. K., Deakins, L. W., Killar, L., Saluk, P. H., Sultzer, B. H. Dissociation of innate susceptibility toSalmonella infection and endotoxin responsiveness in C3HeB/FeJ mice and other strains in the C3H lineage. Infect. Immun. 36 (1982) 696–703.Google Scholar
  28. 28.
    O'Brien, A. D., Rosenstreich, D. L. Genetic control of the susceptibility of C3HeB/FeJ mice toS. typhimurium is regulated by a locus distinct from the knownSalmonella response genes. J. Immunol. 131 (1983) 2613–21615.Google Scholar
  29. 29.
    Oppenheim, J. J., Mizel, S.B., Meltzer, M. S. Biological effects of lymphocyte and MØ-derived mitogenic amplification factors. In:Cohen, S., Pick, E., Oppenheim, J. J. (eds.): Biology of the lymphokines. Academic Press, New York 1979, pp. 291–323.Google Scholar
  30. 30.
    Vogel, S. N., Weedon, L. L., Moore, R. N., Rosenstreich, D. L. Correction of defective macrophage differentiation in C3H/HeJ mice by an interferon-like molecule. J. Immunol. 128 (1982) 380–387.Google Scholar
  31. 31.
    Winberg, J., Andersen, H.-J., Bergström, T., Jacobsen, B., Larson, H., Lincoln, K. Epidemiology of symptomatic urinary tract infection in childhood. Acta Paediatr. Scand. 252 Suppl. (1974) 1–20.Google Scholar

Copyright information

© MMV Medizin Verlag GmbH München 1985

Authors and Affiliations

  • Catharina Svanborg Edén
    • 1
  • L. Hagberg
    • 1
  • D. Briles
    • 2
  • J. McGhee
    • 2
  • S. Michalec
    • 2
  1. 1.Department of Clinical ImmunologyGöteborg
  2. 2.Department of Microbiology and ImmunologyUniversity of Alabama in BirminghamBirminghamUSA

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