Comparative analysis of mycobacterial infections in susceptible I/St and resistant A/Sn inbred mice.
METHODS
The availability and appropriate use of animal models is of significant importance for a better and more detailed understanding of the genetic, immunological and pathological mechanisms underlying the development of mycobacterial disease in humans.


OBJECTIVE
To define a mouse model for tuberculosis severity that can be easily adapted to genetic and immunological analysis of host response to Mycobacterium tuberculosis infection.


METHODS
We describe here two inbred strains of mice, I/St and A/Sn (both Nramp1'), that differ vastly in commonly used parameters of susceptibility to infection with virulent and attenuated strains of M. tuberculosis.


RESULTS
Following infection with a high dose of virulent H37Rv. M. tuberculosis and compared to their resistant A/Sn counterparts, I/St mice displayed more than a 2-fold shorter mean survival time and a more rapid onset and progression of severe body weight loss (cachexia). Moreover, I/St mice supported 20-100-fold higher multiplication of M. tuberculosis following challenge with H37Rv over a large range of infectious inocula. The high susceptibility of I/St mice was also reflected by more severe lung histopathology as evidenced by larger and more numerous lung granuloma and macrophage dominated cellular infiltrates. Finally, we determined that I/St are also unable to control infection with attenuated H37Ra M. tuberculosis and two strains of M. bovis (BCG and Ravenel) indicating hyper-susceptibility of the I/St mouse strain to mycobacterial infections.


CONCLUSIONS
The results of our experiments suggest that comparative analysis of resistant A/Sn and susceptible I/St mice provides an ideal way to study host dependent aspects of tuberculosis susceptibility under the controlled conditions provided by an animal model.
Nikonenko
B V
BV
Department of Immunology, Central Institute for Tuberculosis, Moscow, Russia.
Averbakh
M M
MM
Lavebratt
C
C
Schurr
E
E
Apt
A S
AS
D000818:Animals; D002100:Cachexia / Q000235:genetics / Q000276:immunology; D015169:Colony Count, Microbial; D005260:Female; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology / Q000502:physiology; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012720:Severity of Illness Index; D012737:Sex Factors; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology*