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Genetic factors in host resistance to urinary tract infection

Genetische Faktoren der körpereigenen Abwehr gegen Harnwegsinfektionen

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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 clearence 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.

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 Bakterienwiederfindungsrate 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.

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Authors and Affiliations

  1. Department of Clinical Immunology, Guldhedsgatan 10, S-413 46, Göteborg

    C. Svanborg Edén M.D. & L. Hagberg M.D.

  2. Department of Microbiology and Immunology, University of Alabama in Birmingham, Birmingham, Alabama, U.S.A.

    D. Briles,  J. McGhee &  S. Michalec

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  1. C. Svanborg Edén M.D.
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  3. L. Hagberg M.D.
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  4. J. McGhee
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  5. S. Michalec
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Svanborg Edén, C., Briles, D., Hagberg, L. et al. Genetic factors in host resistance to urinary tract infection. Infection 12, 118–122 (1984). https://doi.org/10.1007/BF01641692

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