Direct comparison of low-dose and Cornell-like models of chronic and reactivation tuberculosis in genetically susceptible I/St and resistant B6 mice.
We applied the low-dose challenge (chronic) and reactivation following chemotherapy withdrawal (Cornell-like) TB models to mouse strains with genetically different susceptibility to and severity of Mycobacterium tuberculosis-triggered disease. Systemic infection caused by intravenous (i.v.) administration of approximately 70 cfus of M. tuberculosis H37Rv lead to chronic, persistent, non-lethal disease in genetically resistant B6 mice, but resulted in a fatal pathological process in the lungs of susceptible I/St animals. Thus, application of the identical experimental approach to genetically different murine hosts allows investigating both slowly progressive disease with the fatal outcome (I/St) and chronic life-span disease (B6). Under Cornell-like model conditions, both temporary eradication of cultivable bacilli from lungs and spleens due to chemotherapy and their re-appearance in organs following its withdrawal were demonstrated in mice of both strains. However, (i) reactivation occurred significantly earlier in I/St than in B6 mice; (ii) I/St mice survived not more than 6 month following chemotherapy withdrawal and demonstrated 100% TB relapse, whereas in B6 mice mortality did not exceed 50%, and no mycobacteria were recovered from some animals. I/St mice, with their genetically determined high TB severity, provide a more reliable tool for modeling TB relapse after chemotherapy withdrawal than mice of more resistant strains.
Radaeva
T V
TV
Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza alley 2, Moscow 107564, Russian Federation.
Nikonenko
B V
BV
Mischenko
V V
VV
Averbakh
M M
MM
Apt
A S
AS
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000995:Antitubercular Agents / Q000627:therapeutic use; D002908:Chronic Disease; D015169:Colony Count, Microbial / Q000379:methods; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D013045:Species Specificity; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D000907:Antibodies, Bacterial; D000995:Antitubercular Agents; D016207:Cytokines