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

Efficacy of Isoniazid Therapy in Mice with Different Genetic Susceptibility to Infection

“…As shown in Figure 3, after 2-mo treatment F1 lungs contained substantially more TB foci, some of which showed clear signs of confluence, whereas in I/St animals lungs were less severe affected by TB inflammation. This is in a sharp contrast with histological picture in the I/St TBaffected lungs in the absence of therapy that we repeatedly observed earlier [19,20]. Thus, mycobacterial growth in the lungs, as well as lung pathology, was more effectively inhibited by INH in genetically susceptible mice.…”

Constitutive Differences in Gene Expression Profiles Parallel Genetic Patterns of Susceptibility to Tuberculosis in Mice

“…Conversely, I/St and A/Sn lung fibroblasts expressed 8-and 50-fold-higher levels of Cxcl-14 than their corresponding lung macrophages. These results show that lung macrophages are major producers of Il-11 and that the high expression levels of Il-11 in macrophages of tuberculosis-susceptible I/St mice compared to expression levels of Il-11 in tuberculosis-resistant A/Sn mice offer a possible explanation for the development of severe pathology in the lungs of M. tuberculosis-infected I/St mice (7,16,18).…”

“…Goya and colleagues (8) have shown that prolonged production of IL-6 in the lungs leads to formation of pulmonary lesions that have lymphoid tissue-like structure, where the chemokine gene Cxcl-13 is highly expressed. Significantly higher expression levels of Il-6 and Cxcl-13 by lung macrophages of susceptible I/St mice (Tables 1 and 2), in conjunction with extremely high levels of specific immunoglobulin G2a antibody responses in these mice (18), strongly suggest that severe TB inflammation in the lungs of these mice involves a nonprotective B-cell component. This suggestion is further supported by a recent finding of Ulrichs et al (25), who demonstrated the formation of well-organized B-cell foci in the vicinity of tuberculous lesions in lung tissue surgically removed from TB patients with a rapidly progressing severe form of the disease.…”

The spectrum of latent tuberculosis: rethinking the biology and intervention strategies

“…In the Cornell mouse model, a latency-like state is drug-induced, resulting in apparent eradication of cultivable bacilli with subsequent occasional spontaneous reactivation 23 . It is possible that some bacterial sub-populations in the Cornell model mimic those present in human latent TB, but in the absence of organized granulomas with caseous necrosis or mineralization, quantitative evaluation of drug efficacy against latent disease in this model is not reliable.…”