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Models for infections in immunodeficiency

thesis
posted on 2024-09-02, 20:19 authored by Anna Berglöf

Increased susceptibility to infections in immunodeficient patients is a well-known phenomenon. The spectrum of infections reflects the underlying defect. Experimental infections in mouse strains with different types of defined immunodeficiencies allow studying the course of infectious diseases in immunocompromised hosts. In such models it is possible to investigate the relationship between immunity and infection and the role of the immune system both in the protection against microorganisms and in the pathogenesis. However, analogous mutations in man and mice do not always result in similar phenotype. Another obstacle is that there is strong host specificity for some microorganisms, and establishment of relevant mouse models for human infections can be a problem. Within this project we have been working with three pathogens: human pathogen Campylobacter jejuni and mouse pathogens polyomavirus and Mycoplasma pulmonis. Several rodent models have been developed in order to mimic human campylobacteriosis but none of them has gained acceptance as universal model of the infection, since it was impossible to produce illness similar to that seen in humans.

The aim of our study (paper I) was to examine the possibility of developing a relevant animal model of campylobacteriosis by infecting scid mice, lacking both B and T cells, with enterotoxin producing C. jejuni strain. In addition, the mice underwent antibiotic treatment prior to infection in order to disrupt the intestinal flora, and enhance gut colonisation. Both immunocompetent controls and scid mice became colonised by C. jejuni for 7 weeks. Any clinical and histological signs of the disease were, however, not observed. This suggests that other factors than normal intestinal flora and acquired immunity must be involved in the resistance of mice to this bacterium.

Mycoplasma infections were performed with M. pulmonis which is a causative agent of murine respiratory disease (papers III, IV, V). M. pulmonis infection in mice resembles in many aspects human disease caused by M. pneumoniae, thus providing a relevant model of the infection. Several mouse strains with severe combined immunodeficiencies (scid/beige, scid), B cell deficiencies (xid, Btk-/-, muMT, lambda5-/-) and immunocompetent control strains of respective backgrounds were infected. Bacteriological, histological and immunological analyses were performed. The results can be summarised to: 1) the course of mycoplasmal disease is highly dependent on the immune status of the host 2) antibodies have a protective role regarding systemic disease, 3) humoral immunity is involved in the pathogenesis of pulmonary lesions, 4) proinflammatory cytokines, locally produced in the chondrocytes, may contribute to the aetiology of Mycoplasma-associated arthritis, 5) different genetic backgrounds of mouse strains influence the severity of the mycoplasmosis.

The importance of antibodies for elimination of polyomavirus infection was also studied (paper II). B cell deficient xid and muMT (referred in the paper as IgM-/-) mice, CD8-/-/muMT double k.o. mice, and normal control mice were infected with polyomavirus as adults. The mice were tested for presence of polyoma DNA with a polyoma specific polymerase chain reaction during 6 weeks post infection. A protective role of antibodies with regard to prevention against persistent polyomavirus infection was shown.

History

Defence date

2002-11-15

Department

  • Department of Laboratory Medicine

Publication year

2002

Thesis type

  • Doctoral thesis

ISBN-10

91-7349-333-3

Language

  • eng

Original publication date

2002-10-25

Author name in thesis

Berglöf, Anna

Original department name

Department of Immunology, Microbiology, Pathology and Infectious Diseases

Place of publication

Stockholm

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