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Direct comparison of low-dose and Cornell-like models of chronic and reactivation tuberculosis in genetically susceptible I/St and resistant B6 mice.

Radaeva TV, Nikonenko BV, Mischenko VV, Averbakh MM, Apt AS

Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza alley 2, Moscow 107564, Russian Federation.

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.

Published 2 February 2005 in Tuberculosis (Edinb), 85(1): 65-72.
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